Obstructive sleep apnea treatment devices, systems and methods

ABSTRACT

In one embodiment, a method for maintaining patency of an upper airway of a patient to treat obstructive sleep apnea may include delivering an electrical stimulation to a portion of a superior laryngeal nerve via a nerve cuff when the nerve cuff is adjacent an external surface of the superior laryngeal nerve, the nerve cuff having a plurality of electrodes, wherein the nerve cuff is configured to be connected to an electrical stimulator via a stimulation lead.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application is a reissue application of U.S. Pat. No.8,428,727 B2, which issued on Apr. 23, 2013, from U.S. patentapplication Ser. No. 13/093,534, filed on Apr. 25, 2011, which is acontinuation of application Ser. U.S. patent application Ser. No.11/907,533, filed on Oct. 12, 2007, of Stephen L. Bolea et al., entitledOBSTRUCTIVE SLEEP APNEA TREATMENT DEVICES, SYSTEMS AND METHODS,currently pending, now U.S. Pat. No. 8,417,343 B2, issued on Apr. 9,2013, which claims the benefits of priority under 35 U.S.C. §§119 and120 to U.S. Provisional Patent Application Nos. 60/851,386 and60/918,257, filed on Oct. 13, 2006, and Mar. 14, 2007, respectively, thedisclosures of all of which are expressly incorporated by referenceherein. The entire contents of these applications are incorporatedherein by reference. This reissue application is related to reissueapplication Ser. No. 14/681,764, filed on Apr. 8, 2015.

FIELD OF THE INVENTION

The inventions described herein relate to devices, systems andassociated methods for treating sleeping disorders. More particularly,the inventions described herein relate to devices, systems and methodsfor treating obstructive sleep apnea.

BACKGROUND OF THE INVENTION

Obstructive sleep apnea (OSA) is highly prevalent, affecting one in fiveadults in the United States. One in fifteen adults has moderate tosevere OSA requiring treatment. Untreated OSA results in reduced qualityof life measures and increased risk of disease including hypertension,stroke, heart disease, etc.

Continuous positive airway pressure (CPAP) is a standard treatment forOSA. While CPAP is non-invasive and highly effective, it is not welltolerated by patients. Patient compliance for CPAP is often reported tobe between 40% and 60%.

Surgical treatment options for OSA are available too. However, they tendto be highly invasive (result in structural changes), irreversible, andhave poor and/or inconsistent efficacy. Even the more effective surgicalprocedures are undesirable because they usually require multipleinvasive and irreversible operations, they may alter a patient'sappearance (e.g., maxillo-mandibulary advancement), and/or they may besocially stigmatic (e.g., tracheostomy).

U.S. Pat. No. 4,830,008 to Meer proposes hypoglossal nerve stimulationas an alternative treatment for OSA. An example of an implantedhypoglossal nerve stimulator for OSA treatment is the Inspire™technology developed by Medtronic, Inc. (Fridely, Minn.). The Inspiredevice is not FDA approved and is not for commercial sale. The Inspiredevice includes an implanted neurostimulator, an implanted nerve cuffelectrode connected to the neurostimulator by a lead, and an implantedintra-thoracic pressure sensor for respiratory feedback and stimulustrigger. The Inspire device was shown to be efficacious (approximately75% response rate as defined by a 50% or more reduction in RDI and apost RDI of ≤20) in an eight patient human clinical study, the resultsof which were published by Schwartz et al. and Eisele et al. However,both authors reported that only three of eight patients remained freefrom device malfunction, thus demonstrating the need for improvements.

SUMMARY OF THE INVENTION

To address this and other unmet needs, the present invention provides,in exemplary non-limiting embodiments, devices, systems and methods fornerve stimulation for OSA therapy as described in the following detaileddescription.

BRIEF DESCRIPTION OF THE DRAWINGS

It is to be understood that both the foregoing summary and the followingdetailed description are exemplary. Together with the following detaileddescription, the drawings illustrate exemplary embodiments and serve toexplain certain principles. In the drawings:

FIG. 1 is a schematic diagram showing a fully implanted neurostimulatorsystem with associated physician programmer and patient controller fortreating obstructive sleep apnea;

FIG. 2 is a schematic diagram showing the implantable components of FIG.1 implanted in a patient;

FIG. 3 is a perspective view of the implantable components shown in FIG.1;

FIG. 4 is a detailed perspective view of the implantable neurostimulator(INS) shown in FIG. 3;

FIG. 5 is a detailed perspective view of the nerve cuff electrode andlead body shown in FIG. 3;

FIG. 5a is an illustration of exemplary movements a lead body may beconfigured to withstand;

FIG. 6 is a close-up detailed perspective view of the nerve cuffelectrode shown in FIG. 3;

FIG. 7 is a detailed perspective view of the internal components of thenerve cuff electrode shown in FIG. 6;

FIG. 8 shows side and end views of an electrode contact of the nervecuff electrode shown in FIG. 7;

FIGS. 9A and 9B are perspective views of the respiration sensing leadshown in FIG. 3;

FIG. 10 schematically illustrates surgical access and tunneling sitesfor implanting the system illustrated in FIG. 2;

FIGS. 11A and 11B schematically illustrate dissection to a hypoglossalnerve;

FIGS. 12 and 12A-12D schematically illustrate various possible nervestimulation sites for activating muscles controlling the upper airway;

FIGS. 13-22 and 22A-22D are schematic illustrations of variousstimulation lead body and electrode designs for use in a neurostimulatorsystem;

FIGS. 23-24 schematically illustrate alternative implant procedures andassociated tools for the stimulation lead;

FIG. 25 schematically illustrates an alternative bifurcated lead bodydesign;

FIGS. 26A-26B schematically illustrate alternative fixation techniquesfor the stimulation lead and electrode cuff;

FIG. 26C schematically illustrates an alternative embodiment of astimulation lead having a fixation mechanism;

FIGS. 27A-27H schematically illustrate field steering embodiments;

FIGS. 27I-27Q schematically illustrate alternative embodiments of nervecuff electrodes with selective fiber stimulation mechanisms;

FIGS. 28-33B schematically illustrate alternative fixation techniquesfor the respiration sensing lead;

FIG. 34 schematically illustrates the distal portion of an exemplaryrespiration sensing lead

FIGS. 35A-35E and 36 schematically illustrate alternative electrodearrangements on the respiration sensing lead;

FIGS. 37 and 37A-37C schematically illustrate various anatomicalpositions or bio-Z vectors for the electrodes on the respiration sensinglead;

FIG. 38A illustrates an exemplary method of sampling a plurality ofvector signals;

FIGS. 38B-46 schematically illustrate alternative respiration signalprocessing techniques;

FIG. 47 schematically illustrates an alternative respiration detectiontechnique;

FIGS. 47A-47D illustrate an exemplary stimulation trigger algorithm;

FIGS. 48-50 schematically illustrate alternative stimulation triggeralgorithms;

FIG. 50A illustrates an exemplary waveform of a patient's respiratorycycle;

FIG. 50B illustrates an exemplary stimulation waveform;

FIGS. 51A-51M are schematic illustrations of various external (partiallyimplanted) neurostimulation systems for treating obstructive sleepapnea;

FIGS. 52A-52G are schematic illustrations of a specific embodiment of anexternal (partially implanted) neurostimulation system;

FIGS. 53-56 schematically illustrate alternative screening tools; and

FIGS. 57A-58B schematically illustrate alternative intra-operativetools.

DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS

The following detailed description should be read with reference to thedrawings in which similar elements in different drawings are numberedthe same. The drawings, which are not necessarily to scale, depictillustrative embodiments and are not intended to limit the scope of theinvention.

Description of Fully Implanted Neurostimulator System

With reference to FIG. 1, a neurostimulator system 10 includingimplanted components 20, physician programmer 30 and patient controller40 is shown schematically. The implanted components of the system 10 maygenerally include an implanted neurostimulator (INS) 50 (a.k.a.,implanted pulse generator (IPG)), an implanted stimulation lead (orleads) 60, and an implanted respiration sensing lead (or leads) 70. TheINS 50 generally includes a header 52 for connection of the leads 60/70,and a hermetically sealed housing 54 for the associated electronics andlong-life or rechargeable battery (not visible). The stimulation lead 60generally includes a lead body 62 with a proximal connector and a distalnerve electrode cuff 64. The respiration sensing lead 70 generallyincludes a lead body 72 with a proximal connector and one or moresensors 74 disposed on or along a distal portion thereof. Suitabledesigns of the INS 50, stimulation lead 60 and respiration sensing lead70 are described in more detail hereinafter.

As shown in FIG. 2, and by way of example, not limitation, the implantedcomponents 20 (shown faded) of the neurostimulator system 10 areimplanted in a patient P with the INS 50 disposed in a subcutaneouspocket, the stimulation lead body 62 disposed in a subcutaneous tunnel,the nerve cuff electrode 64 disposed on a nerve (e.g., hypoglossal nerve(HGN)) innervating a muscle (e.g., genioglossus muscle, not shown)controlling the upper airway, the respiration sensing lead body 72disposed in a subcutaneous tunnel, and the respiration sensors 74disposed adjacent lung tissue and/or intercostal muscles outside thepleural space.

Generally, electrical stimulus is delivered by the INS 50 via thestimulation lead 60 to a nerve innervating a muscle controlling upperairway patency to mitigate obstruction thereof. To reduce nerve andmuscle fatigue, the stimulus may be delivered for only a portion of therespiratory cycle, such as during inspiration which corresponds tonegative pressure in the upper airway. Stimulation may be thus triggeredas a function of respiration as detected by respiration sensing lead 70in a closed-loop feedback system. By way of example, the stimulus may betriggered to turn on at the end of expiration (or at the beginning ofinspiration), and triggered to turn off at the beginning of expiration(or at the end of inspiration). Triggering the stimulus as a function ofexpiration improves capture of the entire inspiratory phase, including abrief pre-inspiratory phase of about 300 milliseconds, thus more closelymimicking normal activation of upper airway dilator muscles.Over-stimulation may cause nerve and/or muscle fatigue, but a 40% to 50%duty cycle may be safely tolerated, thus enabling limitedover-stimulation. As an alternative, stimulus may be deliveredindependent of actual respiration wherein the stimulus duty cycle is setfor an average inspiratory duration at a frequency approximately equalto an average respiratory cycle.

Stimulus may be delivered to one or more of a variety of nerve sites toactivate one muscle or muscle groups controlling patency of the upperairway. For example, stimulation of the genioglossus muscle via thehypoglossal nerve moves or otherwise stiffens the anterior portion ofthe upper airway, thereby decreasing the critical pressure at which theupper airway collapses during inspiration and reducing the likelihood ofan apnea or hypopnea event occurring during sleep. Because the systemsdescribed herein work at the level of the tongue, it may be desirable tocombine this therapy with a therapy (e.g., UPPP or palatal implant) thatwork at the level of the soft palate, thus increasing efficacy for abroader range of patients.

With reference back to FIG. 1, the physician programmer 30 may comprisea computer 32 configured to control and program the INS 50 via awireless link to a programming wand 34. The physician programmer 30 maybe resident in a sleep lab where the patient undergoes apolysomnographic (PSG) study during which the patient sleeps while theINS 50 is programmed to optimize therapy.

The patient controller 40 may comprise control circuitry and associateduser interface to allow the patient to control the system via a wirelesstelemetry link while at home, for example. The patient controller 40 mayinclude a power switch 42 to turn the system on and slowly ramp up whenthe patient goes to sleep at night, and turn it off when the patientwakes in the morning. A snooze switch 44 may be used to temporarily putthe INS 50 in standby mode during which electrical stimulus is pausedfor a preprogrammed period of time to allow the patient to temporarilywake, after which the INS 50 turns back on and ramps up to the desiredstimulus level. A display 46 may be provided to indicate the status ofthe INS 50 (e.g., on, off or standby), to indicate satisfactory wirelesstelemetry link to the INS 50, to indicate remaining battery life of theINS 50, to indicate normal operation of the INS 50, and/or to indicatethe need for patient action etc. Display 46 may be configured to be adash-board-like display, and may be any suitable display available tothose of ordinary skill in the art, such as, for example, an LED or LCDdisplay. Furthermore, information may be communicated to the patientcontroller 40 for display purposes by any suitable means known to thoseof ordinary skill in the art. For example, communication of informationmay be achieved through inductively coupled or radio frequencytelemetry. The patient controller 40 may also have programmability toadjust stimulus parameters (e.g., amplitude) within a pre-set rangedetermined by the physician in order to improve efficacy and/or toreduce sensory perception, for example. Optionally, the patientcontroller 40 may be configured to function as the programming wand 34of the physician programmer 30.

Furthermore, the patient controller 40 may be provided with one or moremechanisms for improving patient compliance. For example, patientcontroller 40 may be provided with a time-keeping mechanism having thecapabilities of a conventional alarm clock. In certain embodiments,controller 40 may be programmed by the user and/or the physician toalert the user when action, such as, for example, turning the system 10on or off, is required by the user. Controller 40 may be configured toalert the user by any suitable means known in the art. For example,controller 40 may emit an audible alarm at programmed time intervals. Inother embodiments, the patient controller 40 may be used to monitor apatient. For example, the patient controller 40 may be programmed toperiodically send reports of patient actions, patient compliance, systemstatus, etc., to a clinician or caregiver via a telephone or computernetwork.

With reference to FIG. 3, the implanted components 20 are shownschematically with more detail. The implanted components include INS 50,stimulation lead 60, and respiration sensing lead 70. The INS 50includes header 52 and housing 54. The stimulation lead 60 includes leadbody 62 and nerve cuff electrode 64. The respiration sensing lead 70includes lead body 72 and respiration sensors 74 (e.g., impedancesensing electrodes).

With reference to FIG. 4, the INS 50 is shown schematically in moredetail. The INS 50 includes header 52 that may be formed usingconventional molding or casting techniques and may comprise conventionalmaterials such as epoxy or polyurethane (e.g., Tecothane brandpolyurethane). The housing 54 may be formed using conventional stampingor forming techniques and may comprise conventional materials such astitanium or ceramic. The housing 54 may include one or more isolatedelectrodes, and/or if a conductive material is used for the housing 54,the housing 54 may comprise an electrode, which may be used forrespiratory sensing, for example. The housing 54 may be hermeticallysealed to the header 52 using conventional techniques. The header 52 mayinclude two or more receptacles for receiving the proximal connectors66/76 of the stimulation lead body 62 and respiration sensing lead body72. The connectors 66/76 may comprise a conventional design such as IS1or other in-line designs. The header 52 may also include set screw sealsand blocks 56 for receiving set screws (not shown) that establishelectrical contact between the INS 50 and the conductors of the leads60/70 via connectors 66/76, and that establish mechanical fixationthereto. Some electrical contact may be achieved through spring type orcam-locked mechanisms. As shown, two set screw arrangements 56 are shownfor the stimulation lead 60 and four set screw arrangements 56 are shownfor the respiration sensing lead 70, but the number may be adjusted forthe number of conductors in each lead. A hole 58 may be provided in theheader 52 for securing the INS 50 to subcutaneous tissue using a sutureat the time of implantation.

The INS 50 may comprise a conventional implanted neurostimulator designused in neurostimulation applications, such as those available fromTexcel (US), CCC (Uruguay) and NeuroTECH (Belgium), but modified for thepresent clinical application in terms of stimulation signal parameters,respiratory signal processing, trigger algorithm, patient control,physician programming, etc. The INS may contain a microprocessor andmemory for storing and processing data and algorithms. Algorithms may bein the form of software and/or firmware, for example. One of severaldifferent embodiments of the neurostimulator may be implemented. Forexample, the neurostimulator may be an internal/implantedneurostimulator (INS) powered by a long-life primary battery orrechargeable battery, or an external neurostimulator (ENS) wirelesslylinked (e.g., inductive) to an implanted receiver unit connected to theleads. The INS (or the receiver unit of the ENS) may be implanted andoptionally anchored in a number of different locations including asubcutaneous pocket in the pectoral region, the dorsal neck region, orcranial region behind the ear, for example.

The INS 50 may include any suitable circuitry and programming inaccordance with the principles of the present disclosure. In oneembodiment, INS 50 may include an activity sensor (not shown) forsensing the activity of a patient, including the amount of activity ofthe patient. The activity sensor may detect motion of a patient by anysuitable means available to those of ordinary skill in the art. Forexample, a patient's motion may be detected by, for example, using aninternal accelerometer and/or measuring the impedance of the patient'storso with, for example, the built-in respiration sensor discussedbelow, and/or measuring a tissue pressure on the surface of theimplanted INS 50.

The data corresponding to a patient's detected motion may be stored,evaluated, and utilized in any of a number of various ways. In oneembodiment, data corresponding to a patient's motion may be used todetermine whether a patient is sleeping or awake. For example, when apatient's activity level falls below a predetermined threshold, it maybe assumed that the patient is sleeping. Conversely, when the patient'sactivity level rises above the pre-determined threshold, it may beassumed that the patient is awake. The activity sensor therefore may beused to facilitate selectively applying treatment when the patient isdetected to be sleeping and/or inhibiting treatment when the patient isdetected to be awake. Alternatively, data corresponding to a patient'smotion may be evaluated over a long period of time, such as, forexample, the first few months of treatment, for indications ofimprovement in a patient's quality of life. It is contemplated thatincreases in a patient's average level of daily activity will correspondto successful treatment of OSA. This, in turn, may correspond toimprovements in the patient's quality of life.

Moreover, the INS 50 may include a long-life battery (not shown) whichrequires periodic replacement after years of service. Alternatively, theINS may include a rechargeable power source such as a rechargeablebattery or super capacitor that is used instead of the long-lifebattery. To facilitate recharging, the INS may include a receiver coilinductively linked to a transmitter coil that is connected to arecharging unit powered by a larger battery or line power. Because thepatient is stationary while sleeping, recharging may be scheduled tooccur sometime during sleep to eliminate the need to carry therecharging unit during daily activities. The transmitter coil and thereceiver coil may be arranged coaxially in parallel planes to maximizeenergy transfer efficiency, and may be held in proximity to each otherby a patch, garment, or other means as described with reference to theexternal neurostimulator embodiments. Other examples of neurostimulatordesigns will be described in more detail hereinafter.

With reference to FIG. 5, the stimulation lead 60 may comprise a varietyof different design embodiments and may be positioned at differentanatomical sites. For example, a nerve cuff electrode(s) 64 may beattached to a nerve(s) innervating musculature affecting patency of theupper airway. As an alternative or in addition, the nerve cuff electrode64 may be replaced with an intramuscular electrode and placed directlyin the musculature affecting patency of the upper airway. The nerveelectrode 64 may be attached to a specific branch of a nerve innervatingthe desired muscle(s), or may be attached to a proximal trunk of thenerve in which a specific fascicle innervating the desired muscle(s) istargeted by steering the stimulus with multiple electrodes. One or moreelectrodes may be used for attachment to one or more portions of nerveson one side (unilateral) of the body, or one or more electrodes may beused for attachment to one or more portions of nerves on both sides(bilateral) of the body. Variations in lead body 62 and electrode 64design as well as variations in the target stimulation site or siteswill be described in more detail hereinafter.

With continued reference to FIG. 5, the lead body 62 may be sigmoidshaped, for example, to reduce strain applied to the cuff electrode 64when the lead body 62 is subject to movement. The sigmoid shape, whichmay alternatively comprise a variety of other waveform shapes, may havea wavelength of approximately 1.0 to 1.5 cm, and an amplitude ofapproximately 0.75 to 1.5 cm, for example. The lead body 62 may comprisea tubular jacket with electrical conductors 68 extending therein. Thetubular jacket may comprise extruded silicone having an outside diameterof approximately 0.047 inches and an inside diameter of approximately0.023 inches, for example. The tubular jacket may optionally have acovering of co-extruded polyurethane, for example, to improvedurability. The conductors 68, shown in a transparent window in thejacket for purposes of illustration only, may comprise a bifilar coil ofinsulated (e.g., ETFE) braided stranded wire (BSW) of MP35NLT material.The number of conductors 68 is shown as two, but may be adjusteddepending on the desired number of independent electrodes used.

The various embodiments of stimulation leads, for example, stimulationlead 60, disclosed herein may be fabricated by any suitable means knownto those having ordinary skill in the art, and may be made from anysuitable material. For example, the discussed sigmoid shape of thetubular jacket of lead body 62 may be formed by first extruding siliconein a semi-cured or semi cross-linked state. Next, the semi cross-linkedextruded tubular jacket may be placed in a sigmoid mold and then allowedto become fully cross-linked. In particular, the semi cross-linkedextruded tubular jacket may be placed in an oven and heated to convertthe semi cross-linked silicone of the extruded tubular jacket to fullycross-linked silicone. Additionally, a lumen within the tubular jacketmay be created along a longitudinal axis of the tubular jacket by anysuitable means.

Furthermore, in accordance with the principles of the presentdisclosure, it is contemplated that one or more of the variousembodiments of stimulation leads disclosed herein may be implanted in ornear highly mobile portions of the body. For example, embodiments of thedisclosed stimulation leads may be implanted in the ventral neck, forexample, along a path between the clavicle and mandible of a patient.Additionally, although mastication, deglutition, and speech may resultin mechanical loading on an implanted stimulation lead, it has beenfound that gross movement of the head and neck may create highmechanical stresses in the conductors of the lead body, lead jacket, andthe junction between the conductor wires and the anchor points, such as,for example, the electrodes. Accordingly, it may be desirable toconfigure the various embodiments of stimulation leads to withstandcertain predetermined amounts of fatigue and/or stresses, which mayresult from mechanical loading on a lead body due to gross movements ofa patient's neck and head.

In particular, research has revealed that approximately 98% of thepopulation may experience a 38.5% elongation or less in the distancebetween the clavicle and angle of the mandible (e.g., adjacent acontemplated area of implantation for a stimulation lead in accordancewith the principles of this disclosure). It has also been found that theangular range of motion of the cervical spine between adjacent vertebraemay be approximately 12 degrees, thereby flexing the lead through thisangle with a bend radius assumed to be approximately 1.0 centimeter. SeeAugustus A. White III et al., Clinical Biomechanics of the Spine, pp.84, 356, and 373 (1978). Furthermore, the frequency of gross headmovement through the range of motion in the contemplated area ofimplantation has been estimated to be approximately 300,000 cycles peryear, or on the average approximately 50 times per waking hour.

Thus, it may be desirable to design a lead body that is capable ofwithstanding, among other things, the stresses imparted by, theabove-noted head and neck movements for an extended amount of time, suchas, for example, ten years. In particular, in order to design a leadbody that may remain functional for the exemplary ten year implantedlife, it may be desirable to configure the lead bodies disclosed hereinto withstand at least the above noted elongation and ranges of motion.For example, since implanted lead bodies are likely to be elongated byat least 38.5%, it may be desirable to design lead bodies to withstandbeing elongated by a predetermined distance Y, such as, for example,approximately 40% (+/−2%) from an initial unstressed state, for aminimum of 3.0 million cycles without failure, as depicted in FIG. 5A.In addition, since it is likely that an implanted lead body mayexperience an angular range of motion of at least 12 degrees, with abend radius of approximately 1.0 centimeter, it may be desirable toconfigure the lead bodies to withstand being flexed around apredetermined radius X, such as, for example, 1.0 centimeter (+/−0.05centimeters), for a predetermined amount of rotation W, such as, forexample, from approximately 0 degrees to approximately 15 degrees (+/−3degrees), such that the 15 degree maximum deflection occurscoincidentally with the maximum elongation of the lead body.

With reference to FIG. 6, the nerve cuff electrode 64 may comprise acuff body 80 having a lateral (or superficial) side 82 and a medial (orcontralateral, or deep) side 84. The medial side 84 is narrower orshorter in length than the lateral side 82 to facilitate insertion ofthe medial side 84 around a nerve such that the medial side is on thedeep side of the nerve and the lateral side is on the superficial sideof the nerve. This configuration reduces the dissection of nervebranches and vascular supply required to get the cuff around a nerve.For the nerve cuff implant sites discussed herein, the medial side 84may have a length of less than 6 mm, and preferably in the range ofapproximately 3 to 5 mm, for example. The lateral side 82 may have alength of more than 6 mm, and preferably in the range of approximately 7to 8 mm, for example. The cuff body 80 may be compliant and may beavailable in different sizes with an inside diameter of approximately2.5 to 3.0 mm or 3.0 to 3.5 mm, for example. The cuff size may also beadjusted depending on the nominal diameter of the nerve at the site ofimplantation. The cuff body 80 may have a wall thickness ofapproximately 1.0 mm and may be formed of molded silicone, for example,and may be reinforced with imbedded fibers or fabrics. An integral towstrap 86 may be used to facilitate wrapping the cuff around a nerve byfirst inserting the strap 86 under and around the deep side of the nerveand subsequently pulling the strap to bring the medial side 84 inposition on the deep side of the nerve and the lateral side 82 on thesuperficial side of the nerve.

With continued reference to FIG. 6, the nerve cuff electrode 64 includeselectrode contacts 90A, 90B, and 90C imbedded in the body 80 of thecuff, with their inside surface facing exposed to establish electricalcontact with a nerve disposed therein. A transverse guarded tri-polarelectrode arrangement is shown by way of example, not limitation,wherein electrode contacts 90A and 90B comprise anodes transverselyguarding electrode contact 90C which comprises a cathode.

With this arrangement, the anode electrodes 90A and 90B are connected toa common conductor 68A imbedded in the body 80, and the cathodeelectrode 90C is connected to an independent conductor 68B extendingfrom the lateral side 82 to the medial side 84 and imbedded in the body80. By using the conductors 68 to make connections within the body 80 ofthe cuff 64, fatigue stresses are imposed on the conductors rather thanthe electrode contacts 90A, 90B and 90C.

With additional reference to FIGS. 7 and 8, the electrode contacts 90A,90B and 90C may thus be semi-circular shaped having an arc length ofless than 180 degrees, and preferably an arc length of approximately 120degrees, for example. Each electrode 90 may have two reverse bends(e.g., hooked or curled) portions 92 to provide mechanical fixation tothe body 80 when imbedded therein. Each electrode 90 may also have twocrimp tabs 94 defining grooves thereunder for crimping to the conductors68 or for providing a passthrough. As shown in FIG. 7, conductor 68Apasses through the grooves under the lower crimp tabs 94 of electrodes90B and 90A, loops 98 around through the grooves under the upper crimptabs 94 of electrodes 90A and 90B, is crimped 96 by the upper tabs 94 ofelectrodes 90A and 90B to provide mechanical and electrical connection,is looped again back between the crimp tabs 94 on the outside of theelectrode contact 90, and is resistance spot welded 95 to provideredundancy in mechanical and electrical connection. Also as shown inFIG. 7, conductor 68B passes through the groove under the lower crimptab 94 of electrode 90C, loops around through the groove under the uppercrimp tab 94 of electrode 90C, and is crimped by the upper tab 94 ofelectrode 90C to provide mechanical and electrical connection. Thisarrangement avoids off-axis tensile loading at the crimp sites 96 whichmay otherwise fail due to stress concentration, and the looped portion98 provides additional strain relief.

FIG. 8 provides example dimensions (inches) of an electrode contact 90for a 2.5 mm inside diameter cuff, wherein the electrode is formed of90/10 or 80/20 platinum iridium alloy formed by wire EDM, for example.As illustrated, and as exemplary and approximate dimensions, electrodecontact 90 may include a surface A having a full radius, a dimension Bof 0.079 inches from tangent to tangent, a dimension C of 0.020 inches(3×), a radius of curvature D of 0.049R with a 16 micro-inch RMS, adimension E of 0.008 inches (2×), a dimension F of 0.0065 inches(+/−0.001 inches) (2×), a dimension G of 0.006 inches (+0.002 inches,−0.001 inches) (2×), a dimension H of 0.014 inches (2×), a dimension Iof 0.010 inches (2×), a dimension J of 0.010 inches (2×), and adimension K of 0.006 inches (+/−0.001 inches).

With reference to FIGS. 9A and 9B, a distal portion of the respirationsensing lead 70 and a distal detail of the sensing lead 70,respectively, are shown schematically. In the illustrated embodiment,the respiration sensing lead 70 and associated sensors 74 are implantedas shown in FIG. 2. However, the respiration sensor(s) may comprise avariety of different design embodiments, both implanted and external,and may be positioned at different anatomical sites. Generally, therespiratory sensor(s) may be internal/implanted or external, and may beconnected to the neurostimulator via a wired or wireless link. Therespiratory sensor(s) may detect respiration directly or a surrogatethereof. The respiratory sensor(s) may measure, for example, respiratoryairflow, respiratory effort (e.g., diaphragmatic or thoracic movement),intra-pleural pressure, lung impedance, respiratory drive, upper airwayEMG, changes in tissue impedance in and around the lung(s) including thelungs, diaphragm and/or liver, acoustic airflow or any of a number otherparameters indicative of respiration. Detailed examples of suitablerespiration sensing leads and sensors will be described in more detailhereinafter.

With continued reference to FIGS. 9A and 9B, the respiration sensinglead 70 includes a lead body 72 and a plurality of respiration sensors74A-74D comprising ring electrodes for sensing bio-impedance. The leadbody 72 of the respiration sensing lead 70 may include a jacket covercomprising an extruded silicone tube optionally including a polyurethanecover (80A durometer), or may comprise an extruded polyurethane tube(55D durometer). The ring electrodes 74A-74D may comprise 90/10 or 80/20platinum iridium alloy tubes having an outside diameter of 0.050 inchesand a length of 5 mm, and secured to the jacket cover by laser weldingand/or adhesive bonding, for example. The lead body 72 may include aplurality of conductors 78 as seen in the transparent window in thejacket cover, which is shown for purposes of illustration only. Theconductors 78 may comprise insulated and coiled BSW or solid wire(optionally DFT silver core wire) disposed in the tubular jacket, withone conductor provided for each ring electrode 74A-74D requiringindependent control. Generally, the impedance electrodes 74A-74D maycomprise current emitting electrodes and voltage sensing electrodes fordetecting respiration by changes in bio-impedance. The number, spacing,anatomical location and function of the impedance electrodes will bedescribed in more detail hereinafter.

System 10 may also include a plurality of diagnostic mechanisms (e.g.,circuitry and/or programming) for monitoring and/or determining thefunctionality of certain components, such as, for example, stimulationlead 60. In particular, system 10 may include one or more switchingcircuits (not shown) that facilitate connection of therespiratory/trans-thoracic impedance sensing circuits of the presentdisclosure (discussed in greater detail below) to stimulation lead 60for measuring the impedance of lead 60. In some embodiments, theimpedance sensing circuit may be connected to each electrode pair. Inother embodiments, the impedance sensing circuit may be connectedbetween the case of the implanted INS 50 and each conductor 68 withinthe lead 60. While those having ordinary skill in the art will readilyrecognize that any suitable impedance sensing method may be utilized tomonitor and/or determine the functionality of lead 60, therespiratory/trans-thoracic impedance sensing circuit of the presentdisclosure may be preferred, since this circuit may be capable ofidentifying small changes in impedance rather than the large changesdetectable by standard methods.

As alluded to above, sensing the impedance of lead 60 may provide formonitoring and/or determining the functionality of lead 60.Specifically, sensing the impedance of lead 60 may facilitate diagnosingand distinguishing between differing types of failures of lead 60. Inparticular, research has revealed that changes in the impedance of lead60 may be indicative of certain types of failures, including, but notlimited to, corrosion, high contact resistance, breakage, and/orshorting. For example, a broken wire inside the lead could be identifiedby an excessively high lead impedance value. Corrosion of an electrodewith its resultant decrease in effective electrode surface area could beidentified by a smaller increase in impedance of that electrode.Similarly, an abnormally low value could correspond with a short betweenconductors in the lead, or an abrasion of the lead body that exposed aconductor to the tissue. Measuring from the case of the INS to eachelectrode allows independent identification of the integrity of eachwire/electrode in the lead. In addition, sensing the impedance of lead60 may facilitate periodic, automated adjustment of stimulation pulseamplitude so as to maintain constant current, energy, and/or chargedelivery using a simpler voltage mode delivery circuit. Such automatedadjustment may facilitate ensuring safety and effectiveness byconsistently delivering the prescribed current, energy, or charge in thepresence of tissue/electrode impedance variations. By consistentlycontrolling the delivery of only the minimally required energy necessaryfor stimulation of the nerve, the stimulation amplitude may beprogrammed closer to the actual stimulation threshold rather thanprogramming a wide margin to ensure continued effectiveness. Thisenhances safety and reduces power consumption. Moreover, sensing theimpedance of lead 60 may allow monitoring of certain system dynamics,such as, for example, doses actually delivered to a patient.

Description of Implant Procedure

With reference to FIG. 10, surgical access sites are schematically shownfor implanting the internal neurostimulator components 20 shown inFIG. 1. The internal neurostimulator components 20 may be surgicallyimplanted in a patient on the right or left side. The right side may bepreferred because it leaves the left side available for implantation ofa pacemaker, defibrillator, etc., which are traditionally implanted onthe left side. The right side may also be preferred because it lendsitself to a clean respiratory signal less susceptible to cardiacartifact and also offers placement of respiratory sensors across theinterface between the lung, diaphragm and liver for better detection ofimpedance changes during respiration.

With continued reference to FIG. 10, the INS (not shown) may beimplanted in a subcutaneous pocket 102 in the pectoral region, forexample. The stimulation lead (not shown) may be implanted in asubcutaneous tunnel 104 along (e.g., over or under) the platysma musclein the neck region. The respiration sensing lead (not shown) may beimplanted in a subcutaneous tunnel 106 extending adjacent the ribcage toan area adjacent lung tissue and/or intercostal muscles outside thepleural space. The nerve cuff electrode (not shown) may be attached to anerve by surgical dissection at a surgical access site 110 proximate thetargeted stimulation site. In the illustrated example, the target nerveis the right hypoglossal nerve and the surgical access site is in thesubmandibular region.

With reference to FIGS. 11A and 11B, a surgical dissection 110 to thehypoglossal nerve is shown schematically. A unilateral dissection isshown, but a bilateral approach for bilateral stimulation may also beemployed. Conventional surgical dissection techniques may be employed.The branch of the hypoglossal nerve (usually a medial or distal branch)leading to the genioglossus muscle may be identified by stimulating thehypoglossal nerve at different locations and observing the tongue forprotrusion. Because elongation and/or flexion may be mistaken forprotrusion, it may be desirable to observe the upper airway using aflexible fiber optic scope (e.g., nasopharyngoscope) inserted into thepatient's nose, through the nasal passages, past the nasopharynx andvelopharynx to view of the oropharynx and hypopharynx and visuallyconfirm an increase in airway caliber by anterior displacement(protrusion) of the tongue base when the nerve branch is stimulated.

The implant procedure may be performed with the patient under generalanesthesia in a hospital setting on an out-patient basis. Alternatively,local anesthesia (at the surgical access sites and along thesubcutaneous tunnels) may be used together with a sedative in a surgicalcenter or physician office setting. As a further alternative, a facialnerve block may be employed. After a post-surgical healing period ofabout several weeks, the patient may return for a polysomnographic (PSG)test or sleep study at a sleep center for programming the system andtitrating the therapy. A trialing period may be employed prior to fullimplantation wherein the hypoglossal nerve or the genioglossus muscle isstimulated with fine wire electrodes in a sleep study and the efficacyof delivering stimulus to the hypoglossal nerve or directly to thegenioglossus muscle is observed and measured by reduction in apneahypopnea index, for example.

Other nerve target sites are described elsewhere herein and may beaccessed by similar surgical access techniques. As an alternative tosurgical dissection, less invasive approaches such as percutaneous orlaparoscopic access techniques may be utilized, making use of associatedtools such as tubular sheaths, trocars, etc.

Description of Alternative Stimulation Target Sites

With reference to FIG. 12, various possible nerve and/or direct musclestimulation sites are shown for stimulating muscles controlling patencyof the upper airway. In addition to the upper airway which generallyincludes the pharyngeal space, other nerves and dilator muscles of thenasal passage and nasopharyngeal space may be selectively targeted forstimulation. A general description of the muscles and nerves suitablefor stimulation follows, of which the pharyngeal nerves and muscles areshown in detail in FIG. 12.

Airway dilator muscles and associated nerves suitable for activationinclude are described in the following text and associated drawings. Thedilator naris muscle functions to widen the anterior nasal aperture(i.e., flares nostrils) and is innervated by the buccal branch of thefacial nerve (cranial nerve VII). The tensor veli palatine musclefunctions to stiffen the soft palate and is innervated by the medial (orinternal) pterygoid branch of the mandibular nerve MN. The genioglossusmuscle is an extrinsic pharyngeal muscle connecting the base of thetongue to the chin and functions to protrude the tongue. Thegenioglossus muscle is typically innervated by a distal or medial branch(or branches) of the right and left hypoglossal nerve. The geniohyoidmuscle connects the hyoid bone to the chin and the sternohyoid muscleattaches the hyoid bone to the sternum. The geniohyoid muscle functionsto pull the hyoid bone anterosuperiorly, the sternohyoid musclefunctions to pull hyoid bone inferiorly, and collectively (i.e.,co-activation) they function to pull the hyoid bone anteriorly. Thegeniohyoid muscle is innervated by the hypoglossal nerve, and thesternohyoid muscle is innervated by the ansa cervicalis nerve.

By way of example, a nerve electrode may be attached to a specificbranch of the hypoglossal nerve innervating the genioglossus muscle(tongue protruder), or may be attached to a more proximal portion (e.g.,trunk) of the hypoglossal nerve in which a specific fascicle innervatingthe genioglossus muscle is targeted by steering the stimulus using anelectrode array. Activating the genioglossus muscle causes the tongue toprotrude thus increasing the size of anterior aspect of the upper airwayor otherwise resisting collapse during inspiration.

As an alternative to activation of any or a combination of the airwaydilator muscles, co-activation of airway dilator and airway restrictoror retruder muscles may be used to stiffen the airway and maintainpatency. By way of example, a nerve electrode may be attached tospecific branches of the hypoglossal nerve innervating the genioglossusmuscle (tongue protruder), in addition to the hyoglossus andstyloglossus muscles (tongue retruders), or may be attached to a moreproximal portion (e.g., trunk) of the hypoglossal nerve in whichspecific fascicles innervating the genioglossus, hyoglossus andstyloglossus muscles are targeted by steering the stimulus using anelectrode array. Activating the hyoglossus and styloglossus musclescauses the tongue to retract, and when co-activated with thegenioglossus, causes the tongue to stiffen thus supporting the anterioraspect of the upper airway and resisting collapse during inspiration.Because the tongue retruder muscles may overbear the tongue protrudermuscle under equal co-activation, unbalanced co-activation may bedesired. Thus, a greater stimulus (e.g., longer stimulation period,larger stimulation amplitude, higher stimulation frequency, etc.) or anearlier initiated stimulus may be delivered to the portion(s) of thehypoglossal nerve innervating the genioglossus muscle than to theportion(s) of the hypoglossal nerve innervating the hyoglossus andstyloglossus muscles.

With continued reference to FIG. 12, examples of suitable nervestimulation sites include B; A+C; A+C+D; B+D; C+D; and E. Sites B and Emay benefit from selective activation by field steering using anelectrode array. As mentioned before, nerve electrodes may be placed atthese target nerve(s) and/or intramuscular electrodes may be placeddirectly in the muscle(s) innervated by the target nerve(s).

Site A is a distal or medial branch of the hypoglossal nerve proximal ofa branch innervating the genioglossus muscle and distal of a branchinnervating the geniohyoid muscle. Site B is a more proximal portion ofthe hypoglossal nerve proximal of the branches innervating thegenioglossus muscle and the geniohyoid muscle, and distal of thebranches innervating the hyoglossus muscle and the styloglossus muscle.Site C is a medial branch of the hypoglossal nerve proximal of a branchinnervating the geniohyoid muscle and distal of branches innervating thehyoglossus muscle and the styloglossus muscle. Site D is a branch of theansa cervicalis nerve distal of the nerve root and innervating thesternohyoid. Site E is a very proximal portion (trunk) of thehypoglossal nerve proximal of the branches innervating the genioglossus,hyoglossus and styloglossus muscles.

Activating site B involves implanting an electrode on a hypoglossalnerve proximal of the branches innervating the genioglossus muscle andthe geniohyoid muscle, and distal of the branches innervating thehyoglossus muscle and the styloglossus muscle.

Co-activating sites A+C involves implanting a first electrode on ahypoglossal nerve proximal of a branch innervating the genioglossusmuscle and distal of a branch innervating the geniohyoid muscle, andimplanting a second electrode on the hypoglossal nerve proximal of abranch innervating the geniohyoid muscle and distal of branchesinnervating the hyoglossus muscle and the styloglossus muscle.

Co-activating sites A+C+D involves implanting a first electrode on ahypoglossal nerve proximal of a branch innervating the genioglossusmuscle and distal of a branch innervating the geniohyoid muscle;implanting a second electrode on the hypoglossal nerve proximal of abranch innervating the geniohyoid muscle and distal of branchesinnervating the hyoglossus muscle and the styloglossus muscle; andimplanting a third electrode on a branch of an ansa cervicalis nervedistal of the nerve root and innervating the stemohyoid.

Co-activating sites B+D involves implanting a first electrode on ahypoglossal nerve proximal of branches innervating the genioglossusmuscle and the geniohyoid muscle, and distal of branches innervating thehyoglossus muscle and the styloglossus muscle; and implanting a secondelectrode on a branch of an ansa cervicalis nerve distal of the nerveroot and innervating the sternohyoid.

Co-activating sites C+D involves implanting a first electrode on ahypoglossal nerve proximal of a branch innervating the geniohyoidmuscle, and distal of branches innervating the hyoglossus muscle and thestyloglossus muscle and implanting a second electrode on a branch of anansa cervicalis nerve distal of the nerve root and innervating thesternohyoid.

Activating site E involves implanting an electrode on a hypoglossalnerve proximal of the branches innervating the genioglossus, hyoglossusand styloglossus muscles; and selectively activating (e.g., by fieldsteering) the genioglossus muscle before or more than the hyoglossus andstyloglossus muscles.

With reference now to FIGS. 12A-12D, additional possible nervestimulation sites are shown for effecting muscles controlling patency ofthe upper airway. For example, the cranial root of the accessory nerveAN (cranial nerve XI) innervates the levator veli palatini muscle of thesoft palate, which elevates the soft palate. The cranial root of theaccessory nerve AN also innervates the palatoglossal muscle, whichfunctions to pull the soft palate inferiorly when the genioglossus isco-activated via the hypoglossal nerve (HGN). Moreover, because thecranial root of the accessory nerve AN also innervates various othermuscles including, but not limited to, the palatopharyngeus, specificfibers in the accessory nerve AN may be selectively stimulated with oneor more of the fiber selective stimulation means described in greaterdetail below, in order to only activate desired fibers of the nerve. Theglossopharyngeal nerve GN (cranial nerve IX) innervates thestylopharyngeus, which functions to dilate the lateral walls of thepharynx. However, since the glossopharyngeal nerve GN is amulti-function nerve with both afferent and efferent fibers, one or moreof the fiber selective stimulation means described in greater detailbelow may be used to facilitate targeting the fibers that innervate onlythe stylopharyngeus. The cranial root of the accessory nerve AN and theglossopharyngeal nerve GN may be singularly activated, or these nervesmay be co-activated with other nerve sites, such as, for example, thehypoglossal nerve, for increased efficacy.

Another possible nerve stimulation site may include the superiorlaryngeal nerve SLN. The superior laryngeal nerve SLN descends posteriorand medial from the internal carotid artery and divides into theinternal laryngeal nerve ILN and external laryngeal nerve ELN. While theexternal laryngeal nerve ELN descends behind the sternohyoid with thesuperior thyroid artery, the internal laryngeal nerve ILN descends nearthe superior laryngeal artery. The internal laryngeal nerve ILN containssensory (afferent) fibers that are connected to receptors in the larynx.Some of these receptors include, but are not limited to,mechanoreceptors which detect pressure changes in a patient's upperairway associated with its collapse and institute a physiologicalresponse to re-open the patient's upper airway. Therefore, stimulationof specific afferent fibers inside the ILN nerve may result intriggering a reflex response that causes upper airway dilation byactivating several muscles groups.

As discussed below, the superior laryngeal nerve SLN, in addition tobeing a sensory nerve, is also a motor nerve. Therefore, it iscontemplated that one or more of the fiber selective stimulation meansdescribed in greater detail below may be utilized to facilitate onlystimulating the sensory or afferent fibers of the nerve.

Description of Alternative Nerve Electrodes

Any of the alternative nerve electrode designs described hereinafter maybe employed in the systems described herein, with modifications toposition, orientation, arrangement, integration, etc. made as dictatedby the particular embodiment employed. Examples of other nerve electrodedesigns are described in U.S. Pat. No. 5,531,778, to Maschino et al.,U.S. Pat. No. 4,979,511 to Terry, Jr., and U.S. Pat. No. 4,573,481 toBullara, the entire disclosures of which are incorporated herein byreference.

With reference to the following figures, various alternative electrodedesigns for use in the systems described above are schematicallyillustrated. In each of the embodiments, by way of example, notlimitation, the lead body and electrode cuff may comprise the same orsimilar materials formed in the same or similar manner as describedpreviously. For example, the lead body may comprise a polymeric jacketformed of silicone, polyurethane, or a co-extrusion thereof. The jacketmay contain insulated wire conductors made from BSW or solid wirecomprising MP35N, MP35N with Ag core, stainless steel or Tantalum, amongothers. The lead body may be sigmoid shaped to accommodate neck andmandibular movement. Also, a guarded cathode tri-polar electrodearrangement (e.g., anode-cathode-anode) may be used, with the electrodesmade of 90/10 or 80/20 PtIr alloy with silicone or polyurethane backing.

With specific reference to FIGS. 13A and 13B, a self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 13A shows a perspective view of a nerve electrodecuff 130 on a nerve such as a hypoglossal nerve, and FIG. 13B shows across-sectional view of the nerve cuff electrode 130 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 130 comprises acompliant sheet wrap 132 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet by sutures138, for example. The sheet 132 includes a plurality of radially andlongitudinally distributed fenestrations 134 to allow expansion of thesheet 132 to accommodate nerve swelling and/or over tightening.Electrode contacts 136 comprising a coil, foil strip, conductiveelastomer or individual solid conductors may be carried by the sheet 132with an exposed inside surface to establish electrical contact with thenerve.

With specific reference to FIGS. 14A-14C, another self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 14A shows a perspective view of a nerve electrodecuff 140 on a nerve such as a hypoglossal nerve, and FIG. 14B shows across-sectional view of the nerve cuff electrode 140 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 140 comprises acompliant sheet wrap 142 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet by sutures148A, or by a buckle 148B as shown in FIG. 14C, for example. Theopposite portions of the sheet 142 comprise one or more narrow strips144 integral with the sheet 142 to allow expansion and to accommodatenerve swelling and/or over tightening. Electrode contacts 146 comprisinga coil, foil strip, conductive elastomer or individual solid conductorsmay be carried by the sheet 142 with an exposed inside surface toestablish electrical contact with the nerve.

With specific reference to FIGS. 15A-15C, another self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 15A shows a perspective view of a nerve electrodecuff 150 on a nerve such as a hypoglossal nerve, and FIG. 15B shows across-sectional view of the nerve cuff electrode 150 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 150 comprises acompliant sheet wrap 152 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet 152 bysutures 158, for example. The opposite portions of the sheet 152 areoffset from the nerve and a thickened portion of the sheet 152 fills theoffset space. The offset distance reduces the amount of compressiveforce that the electrode cuff can exert on the nerve. To further reducethe pressure on the nerve, the sheet 152 includes a plurality ofradially distributed slits 154 extending partly through the thickness ofthe sheet 152 to allow expansion and to accommodate nerve swellingand/or over tightening.

With specific reference to FIGS. 16A and 16B, another self-sizing andexpandable design is shown to accommodate nerve swelling and/orover-tightening. FIG. 16A shows a perspective view of a nerve electrodecuff 160 on a nerve such as a hypoglossal nerve, and FIG. 16B shows across-sectional view of the nerve cuff electrode 160 on the nerve. Inthis embodiment, the implantable nerve cuff electrode 160 comprises acompliant sheet wrap 162 configured to be wrapped about a nerve andsecured thereto by connecting opposite portions of the sheet 162 bysutures 168, for example. The sheet 162 includes a plurality of radiallydistributed and longitudinally extending convolutions 164 that maycomprise alternative thick 164A and thin 164B portions in the sheet 162and/or overlapping portions 164C of the sheet 162 to allow expansion andto accommodate nerve swelling and/or over tightening. Electrode contacts166 comprising a coil, foil strip, conductive elastomer or individualsolid conductors may be carried by the sheet 162 with an exposed insidesurface to establish electrical contact with the nerve. Nerve cuffelectrode 160 may accommodate one or two lead bodies 62A, 62B forconnection to the electrode contacts 166 on the same or opposite sidesof the nerve.

Turning now to FIGS. 16C-16D, additional self-sizing and expandabledesigns are shown to accommodate nerve swelling and/or over-tightening.With specific reference to FIG. 16C, there is depicted a nerve cuffelectrode 1600 having a cuff body with a relatively widesemi-cylindrical lateral side 1601 and a plurality of opposing arms 1602extending thereform for placement on the deep (contralateral) side ofthe nerve. Although the embodiment depicted in FIG. 16C includes twosuch opposing arms 1602, nerve cuff electrode 1600 may include anysuitable number of opposing arms 1602. Lateral side 1601 may include anarray of electrode contacts 1603. For example, in the depictedembodiment, lateral side may include three electrode contacts 1603. Thethree electrode contacts 1603 may include one cathode electrode contact1603 disposed between two anode electrode contacts 1603, as shown.

Arms 1602 may be secured around a nerve (not shown) by any suitablemeans. For example, it is contemplated that arms 1602 may be elastic innature, so as to gently grasp the nerve on its deep (contralateral)side. Alternatively, arms 1602 may be actively secured about a nerve by,for example, suturing an end portion of arms 1602 to, e.g., a portion oflateral side 1601. In embodiments where arms 1602 may be activelysecured about a nerve, arms 1602 may be provided with a safety mechanism(not shown) that permits nerve cuff electrode 1600 to become disengagedfrom a nerve it is secured about upon the application of a predeterminedamount of force. This predetermined force will be established at a levelthat is below that which can cause damage to the nerve.

As shown in FIG. 16D, opposing arms 1602 may be configured to expandand/or deform as necessary, in order to accommodate nerve swellingcaused by, for example, localized trauma inflicted upon the nerve duringcuff implantation. For example, each of opposing arms 1602 may have anunattached terminal end 1602a. In order to facilitate expansion,opposing arms 1602 may be also made from any suitable material known tothose having ordinary skill in the art. For example, arms 1602 may bemade from an elastomer, such as, for example, silicone or polyurethane.Additionally, one or both of arms 1602 may be provided with one or morelimiting mechanisms (not shown) to limit the amount of expansion arms1602 may undergo as a result of, for example, nerve swelling. Suchlimiting mechanisms may include any suitable mechanism, including, butnot limited to, flanges, barbs, and/or sutures.

With reference to FIG. 16E, there is depicted another design of aself-sizing and expandable nerve cuff electrode 1610. For the purposesof this disclosure, nerve cuff electrode 1610 may be substantiallysimilar to nerve cuff electrode 1600 depicted in FIGS. 16C-16D. Nervecuff electrode 1610, however, may differ from nerve cuff electrode 1600in at least two significant ways. First, for example, lateral side 1611of nerve cuff electrode 1610 may carry two anode electrode contacts 1613and the medial side 1612 may carry one cathode electrode contact 1613 inan arrangement that may be referred to as transverse guarded tri-polar.Second, for example, nerve cuff electrode 1610 may include three arms1614-1616 extending from lateral side 1611. In the depicted embodiment,arms 1614 and 1616 may be configured to extend substantially in the samedirection from the same edge 1611a of lateral side 1611, while arm 1615may be configured to extend in substantially the opposing direction froman opposing edge 1611b of lateral side 1611. In the depicted embodiment,arm 1615 may be disposed between arms 1614 and 1616, and may beconfigured to carry the cathode electrode contact 1613, as mentionedabove. However, any suitable arrangement of arms 1614-1616 and/orelectrode contacts 1613 may be utilized within the principles of thisdisclosure.

As shown in FIG. 16F, certain embodiments of nerve curve electrode 1600and/or nerve cuff electrode 1610 may include one or more elongated arms1617. Arms 1617 may include any suitable length, so as to allow arms1617 to wrap around a body portion of the cuff electrode one or moretimes in a spiral-like fashion, when the cuff electrode is mounted aboutan un-swollen nerve. However, arms 1617 may allow the cuff electrode toremain mounted on the nerve as it accommodates large amounts of nerveswelling by unraveling and/or unwrapping as the nerve swells. Forexample, each of the arms 1617 may overlap lateral side 1601 or 1611 toaccommodate larger amounts of nerve swelling without allowing the cuffto become detached from the nerve. The elongated arms 1617 may extendaround the body of the cuff electrode to form a spiral when the nerve isin a substantially unswollen state, as shown.

With reference to FIG. 17, a modular nerve electrode cuff 170 is shownthat includes a semi-cylindrical body portion 172 with an array ofelectrode contacts 176 with separate insulative strips 174 for placementon the deep (contralateral side) of the nerve, which typically has morenerve branches and connecting blood vessels. In this embodiment,independent placement of the electrode body 172 on the superficial(lateral) side of the nerve and placement of the insulative strips 174on the deep (contralateral) side of the nerve minimizes dissection. Thestrips 174 may be connected to the electrode body 172 by sutures orbuckles as described previously. This embodiment is also self-sizing toaccommodate nerve swelling and/or over-tightening.

With reference to FIG. 18, a nerve cuff electrode 180 is shown that hasa cuff body with a relatively wide semi-cylindrical lateral side 182 anda relatively narrow semi-cylindrical medial side 184 that may extendthrough a small fenestration around the deep (contralateral) side of anerve to securely and gently grasp the nerve while minimizingdissection. In the illustrated example, the lateral side 182 carries twoanode electrode contacts 186 and the medial side 184 carries one cathodeelectrode contact 186 in an arrangement that may be referred to astransverse guarded tri-polar. A tow strap 188 is provided for insertingthe medial side 184 around the deep side of the nerve. The tow strap 188may be integrally formed with the medial side 184 of the cuff body, andmay include a reinforced tip 188A with a serrated or marked cut line188B.

With reference to FIGS. 19A and 19B, a nerve cuff electrode 190 is shownthat has a cuff body with a relatively wide semi-cylindrical lateralside 192 and a relatively narrow semi-cylindrical medial side 194 thatmay extend through a small fenestration around the deep (contralateral)side of a nerve to securely and gently grasp the nerve while minimizingdissection. In the illustrated example, the lateral side 192 carries onecathode electrode contact 196C and two guarding anode electrode contacts196B and 196D, and the medial side 194 carries one anode electrodecontact 196A in an arrangement that may be referred to as transverse andlongitudinal guarded quad-polar. The provision of guarding electrodecontacts 196B and 196C reduces extrinsic stimulation due to the lack ofinsulative material on the medial side 194. The embodiments of FIGS. 18,19A and 19B illustrate two different electrode contact arrangements, butthe number and arrangement may be modified to suit the particularapplication.

With reference to FIG. 20, a nerve cuff electrode array 200 is shownthat utilizes a series of relatively narrow independent cuffs 200A, 200Band 200C with corresponding independent lead bodies 62. Providing aseries of relatively narrow independent cuffs 200A, 200B and 200Cminimizes the required dissection around the nerve for implantationthereof. Also, the series of independent cuffs 200A, 200B and 200Callows more selectivity in electrode placement to adjust for anatomicalvariation or multiple target stimulation sites, for example. Providingmultiple independent lead bodies 62 allows for more options in routingand placement of the individual lead bodies 62 (e.g., alternateplacement of lead body 62A) and also prevents tissue encapsulationaround the lead bodies 62 from collectively affecting encapsulation ofthe nerve cuffs 200. Each of the cuffs 200A, 200B and 200C may include acuff body 202 with one or more imbedded electrode contacts (not shown)and a tow strap 204 as described before. Also, each of the cuffs 200A,200B and 200C may include suture 208 or a buckle 206 to lock onto thetow strap 204 for connecting opposite ends of the body 202 around thenerve.

With reference to FIGS. 21A and 21B, a nerve cuff electrode 210 is shownwith multiple electrode contacts 216 radially spaced around the insidesurface of a compliant split cuff body 212 to establish multipleelectrical contact points around the circumference of the nerve. Each ofthe electrode contacts 216 may be connected to independent conductors inthe lead body 62 via axially extending wires 217. This arrangementallows for field steering as discussed herein. The compliant split cuffbody 212 together with axially extending wires 217 allows forself-sizing to accommodate nerve swelling and/or over-tightening. One ormore pairs of tabs 214 extending from opposite end portions of the cuffbody 212 may be connected by a suture (not shown) as described herein.As shown in FIG. 21B, the proximal and distal ends of the cuff body 212may have tapered thickness extensions 218 to provide strain relief andreduce mechanical irritation of the nerve due to contact with the edgeof the cuff.

With reference to FIG. 22, a nerve cuff electrode 220 is shown with aseparable lead 62 in what may be referred to as a modular design. Inthis embodiment, the nerve cuff electrode 220 includes a semi-circularflexible cuff body (or housing) 222 with a receptacle 224 configured toaccommodate a distal end of a lead body 62 therein. The receptacle 224may provide a releasable mechanical lock to the lead body 52 as by apress fit, mating detents, etc. The distal end of the lead body 62carries an array of ring electrodes 65, with windows 226 provided in thecuff body 222 configured to align with the ring electrodes 65 and permitexposure of the ring electrodes 65 to the nerve to establish electricalconnection therebetween. The cuff body 222 may be attached to the nerveor simply placed adjacent the nerve. Any of the cuff designs describedherein may be provided with a receptacle to accommodate a removable leadbody. This embodiment allows postoperative removal of the lead body 62without removal of the cuff 220, which may be beneficial in revisionoperations, for example.

Turning now to FIG. 22A, there is depicted another design for a nervecuff electrode 2000 where a substantially cylindrical distal portion 62′of lead body 62 carries an array of electrodes 2001. Electrodes 2001 mayinclude ring electrodes that extend completely around the circumferenceof lead body 62, or, alternatively, may include generally semi-circularelectrodes that extend partially around the circumference of lead body62. The electrode may be selectively insulated on any portion of itssurface to allow directional stimulation. Nerve cuff electrode 2000 mayfurther include a nerve securing mechanism for securing lead body 62 toa nerve, such as, for example, a hypoglossal nerve. The nerve securingmechanism may include, for example, a compliant sheet wrap 2002 that isattached on one end to a distal portion of lead body 62, and unattachedon the other opposing end. Compliant sheet wrap 2002 may be attached tolead body 62 by any suitable means.

As shown in FIG. 22B, compliant sheet wrap 2002 may be configured to bewrapped around a nerve and secured thereto by, for example, connectingopposite portions of the sheet wrap 2002 together. Sheet wrap 2002 maybe provided with one or more features to facilitate such connections.For example, it is contemplated that a portion 2002b of sheet wrap 2002that is closest to lead body 62 may be provided with a projection 2002cthat is configured for insertion into a corresponding opening 2002eprovided on a portion 2002d of sheet wrap 2002 that is opposite portion2002b. Opening 2002e may be configured to retain projection 2002cdespite the forces exerted on sheet wrap 2002 during normal nerveswelling. However, opening 2002e may be configured to release projection2002c when forces greater than a predetermined threshold are exerted onsheet wrap 2002, so as to prevent injury to the nerve. As shown in FIG.22C, in some embodiments, opening 2002e may be provided as a slot,which, in addition to securing projection 2002c, may allow projection2002c to slide within the opening 2002e, thereby allowing expansion ofthe sheet wrap 2002 to accommodate nerve swelling and/or over tighteningof the sheet wrap 2002. Additionally, both portions 2002b and 2002d maybe provided with suitable openings to facilitate the insertion ofsutures (not shown) or other suitable fastening mechanisms. Sheet wrap2002 may have any desired width. For example, sheet wrap 2002 may have asubstantially tapered width, in order to securely wrap the nerve whileminimizing dissection.

Compliant sheet wrap 2002 may be provided with any of a number of meansthat allow sheet wrap 2002 to expand, in order to accommodate nerveswelling and/or over tightening. For example, in one embodiment, sheetwrap 2002 may be provided with a plurality of radially and/orlongitudinally distributed fenestrations (not shown). In otherembodiments, sheet wrap 2002 may be provided with a plurality ofundulations 2002a, such as, for example, sigmoid undulations, which mayallow for expansion of sheet wrap 2002.

With reference now to FIG. 22D, there is depicted another design for anerve cuff electrode 2200 where a distal portion 62″ of lead body 62carries an array of electrodes 2201. For the purposes of thisdisclosure, nerve cuff electrode 2200 may include substantially the samefeatures as nerve cuff electrode 2000 depicted in FIGS. 22A-22C. Nervecuff electrode 2200, however, may differ from nerve cuff electrode 2000in that distal portion 62″ may be substantially flat or paddle-shaped.Furthermore, electrode contacts 2201, rather than being circular orsemi-circular in configuration, may be substantially flat inconfiguration. In certain procedures, it is contemplated that thepaddle-shaped distal portion 62″, along with the substantially flatelectrode contacts 2201, may promote greater contact between electrodecontacts 2201 and the nerve they are mounted upon.

Description of Alternative Implant Procedure for the Stimulation Lead

With reference to FIGS. 23A-23C, an insertable paddle-shaped lead 230design is shown. The insertable lead 230 may have a paddle-shape(rectangular) cross-section with a tubular jacket 232 and one or moreconductors 234 extending therethrough to one or more distally placedelectrode contact(s) 236. The electrode contact(s) 236 may be imbeddedin a molded distal end of the jacket 232 such that the electrode contact236 has an exposed surface to face the nerve when implanted as shown inFIG. 23B. The space between the nerve and electrode is shown forpurposes of illustration only, as the electrodes may be placed in directcontact with the nerve. Soft tines 238 may be integrally formed at thedistal end of the tubular jacket 232 for purposes of mild fixation totissue when implanted. The insertable lead 230 is configured to beplaced adjacent to the nerve (thereby negating the need for a cuff) byinserting the lead 230 at the surgical access site 110 and following thenerve distally until the electrode contacts 236 are placed adjacent thetarget stimulation site. The insertable lead 232 may be used alone or inconjunction with another lead as shown in FIGS. 23B and 23C. In theillustrated example, a first lead 230A is inserted along a superficialside of the nerve and a second lead 230B is inserted along a deep sideof the nerve.

A method of implanting lead 230 may generally comprise accessing aproximal extent of the nerve by minimal surgical dissection andretraction of the mylohyoid muscle as shown in FIG. 23C. Special toolsmay alternatively be employed for percutaneous or laparoscopic access asshown and described with reference to FIGS. 24A-24C. Subsequently, twopaddle-shaped leads 230 with distal electrode contacts 236 may beinserted into the surgical access site and advanced beyond the accesssite along a distal aspect of the nerve to the desired stimulation siteon either side of the nerve. These techniques minimize trauma andfacilitate rapid recovery.

A less invasive method of implanting a paddle-shaped lead 230 is shownin FIGS. 24A-24C. In this embodiment, a rectangular tubular trocar 240with a sharpened curved tip is placed through a percutaneous access site111 until a distal end thereof is adjacent the superficial side of thenerve. A paddle-shaped lead 230 is inserted through the lumen of thetrocar 240 and advanced distally beyond the distal end of the trocar 240along the nerve, until the electrode contacts 236 are positioned at thetarget stimulation site. As shown in FIG. 24B, which is a view takenalong line A-A in FIG. 24A, the insertable lead 230 includes multipleelectrode contacts 236 in an anode-cathode-anode arrangement, forexample, on one side thereof to face the nerve when implanted. In thisembodiment, tines are omitted to facilitate smooth passage of the lead230 through the trocar. To establish fixation around the nerve and toprovide electrical insulation, a backer strap 242 of insulative materialmay be placed around the deep side of the nerve. To facilitatepercutaneous insertion of the backer 242, a curved tip needle 244 may beinserted through a percutaneous access site until the tip is adjacentthe nerve near the target stimulation site. A guide wire 246 with aJ-shaped tip may then be inserted through the needle 244 and around thenerve. The backer 242 may then be towed around using the guide wire 246as a leader, and secured in place by a buckle (not shown), for example.

With reference to FIG. 25, a bifurcated lead 250 is shown to facilitateseparate attachment of electrode cuffs 64 to different branches of thesame nerve or different nerves for purposes described previously. Any ofthe nerve cuff electrode or intramuscular electrode designs describedherein may be used with the bifurcated lead 250 as shown. In theillustrated example, a first lead furcation 252 and a second leadfurcation 254 are shown merging into a common lead body 62. Eachfurcation 252 and 254 may be the same or similar construction as thelead body 62, with modification in the number of conductors. More thantwo electrode cuffs 64 may be utilized with corresponding number of leadfurcations.

Description of Stimulation Lead Anchoring Alternatives

With reference to FIGS. 26A and 26B, an elastic tether 264 with alimited length is utilized to prevent high levels of traction on theelectrode cuff 64 around the hypoglossal nerve (or other nerve in thearea) resulting from gross head movement. In other words, tether 264relieves stress applied to the electrode cuff 64 by the lead body 62.FIGS. 26A and 26B are detailed views of the area around the dissectionto the hypoglossal nerve, showing alternative embodiments of attachmentof the tether 264. The proximal end of the tether 264 may be attached tothe lead body 62 as shown in FIG. 26A or attached to the electrode cuff64 as shown in FIG. 26B. The distal end of the tether 264 may beattached to the fibrous loop carrying the digastrics tendon as shown inFIG. 26A or attached to adjacent musculature as shown in FIG. 26B.

By way of example, not limitation, and as shown in FIG. 26A, a tubularcollar 262 is disposed on the lead body 62 to provide connection of thetether 264 to the lead body 62 such that the lead body 62 is effectivelyattached via suture 266 and tether 264 to the fibrous loop surroundingthe digastrics tendon. The tether 264 allows movement of the attachmentpoint to the lead body 62 (i.e., at collar 262) until the tether 264 isstraight. At this point, any significant tensile load in the caudaldirection will be borne on the fibrous loop and not on the electrodecuff 64 or nerve. This is especially advantageous during healing beforea fibrous sheath has formed around the lead body 62 and electrode cuff64, thus ensuring that the cuff 64 will not be pulled off of the nerve.It should be noted that the length of the tether 262 may be less thanthe length of the lead body 62 between the attachment point (i.e., atcollar 262) and the cuff 64 when the tensile load builds significantlydue to elongation of this section of lead body 62.

The tether 264 may be formed from a sigmoid length of braided permanentsuture coated with an elastomer (such as silicone or polyurethane) tomaintain the sigmoid shape when in the unloaded state. The tether 264may also be made from a monofilament suture thermoformed or molded intoa sigmoid shape. The distal end of the tether 264 may be attached to thefibrous loop using a suture 266 or staple or other secure means. Notethat the tether 264 may be made from a biodegradable suture that willremain in place only during healing.

Also by way of example, not limitation, an alternative is shown in FIG.26B wherein the tether 264 is attached to the electrode cuff 64. Thedistal end of the tether 264 may be attached to the adjacent musculatureby suture 266 such the musculature innervated by branches of thehypoglossal nerve or other musculature in the area where the electrodecuff 64 is attached to the nerve. The tether 264 ensures that theelectrode cuff 64 and the hypoglossal nerve are free to move relative tothe adjacent musculature (e.g., hyoglossal). As significant tensile loadis applied to the lead body 62 due to gross head movement, the tether264 will straighten, transmitting load to the muscle rather then to thenerve or electrode cuff 64.

As alluded to above, stimulation lead 60 may comprise a number ofdiffering design embodiments. One such embodiment has been discussedabove with respect to FIG. 5. Another such embodiment is depicted inFIG. 26C, which illustrates a stimulation lead 2600. Stimulation lead2600 may be substantially similar to and/or may include one or more ofthe features described in connection with stimulation lead 60. As shownin FIG. 26C, stimulation lead 2600 may include a lead body 2662 having afirst, proximal lead body portion 2663. First lead body portion 2663 maybe substantially similar to lead body 62. For example, first lead bodyportion 2663 may include a similar flexibility as lead body 62. Leadbody 2662 may further include a second, distal lead body portion 2664leading to the distal end of lead body 2662 at the nerve cuff electrode.Second lead body portion 2664 may include a material property that isdifferent than lead body portion 2663, such as, for example, a greaterflexibility, in order to accommodate stresses imparted upon lead body2662 by a nerve cuff electrode and movement of the patient's head, neck,and other neighboring body portions. The highly flexible distal portion2664 reduces the stress (torque and tension) imparted by lead body 2662on the electrode cuff, thereby reducing the likelihood that the cuffwill be detached from the nerve or damage the nerve.

Lead body portion 2664 may be made more flexible than lead body portion2663 by any of a variety of ways. For example, lead body portion 2664may be made from a material having differing flexibility. Alternatively,the diameters of the braided stranded wires (BSW) and/or wire insulationthat make up the lead body portion 2664 may be reduced when possible.

With continuing reference to FIG. 26C, stimulation lead 2600 may furtherinclude an anchor 2665 operably connected to lead body 2662. Althoughanchor 2665 in the illustrated embodiment is depicted as being disposedin between lead body portions 2663 and 2664, anchor 2665 may be disposedat any suitable location along the length of lead body 2662.Furthermore, anchor 2665 may be fixedly or movably connected to leadbody 2662.

Anchor 2665 may include any suitable configuration known in the art. Forexample, anchor 2665 may include a substantially flat body portion 2666.Body portion 2666 may be configured to be secured to tissue, such as,for example, tissue proximate a treatment site, by any suitable meansavailable in the art. For example, body portion 2666 may be providedwith openings 2667 to facilitate, for example, suturing anchor 2665 tonearby tissue. Anchor 2665 can thereby isolate stress (tension) to oneportion of lead body 2662, and particularly portion 2663, caused bygross head and neck movement.

Description of Field Steering Alternatives

With reference to FIGS. 27A-27G, a field steering nerve cuff electrode64 is shown schematically. As seen in FIG. 27A, the nerve cuff electrode64 may include four electrode contacts 90A-90D to enable field steering,and various arrangements of the electrode contacts 90A-90D are shown inFIGS. 27B-27G. Each of FIGS. 27B-27G includes a top view of the cuff 64to schematically illustrate the electrical field (activating function)and an end view of the cuff 64 to schematically illustrate the area ofthe nerve effectively stimulated. With this approach, electrical fieldsteering may be used to stimulate a select area or fascicle(s) within anerve or nerve bundle to activate select muscle groups as describedherein.

With specific reference to FIG. 27A, the nerve cuff electrode 64 maycomprise a cuff body having a lateral (or superficial) side 82 and amedial (or contralateral, or deep) side 84. The medial side 84 isnarrower or shorter in length than the lateral side 82 to facilitateinsertion of the medial side 84 around a nerve such that the medial sideis on the deep side of the nerve and the lateral side is on thesuperficial side of the nerve. An integral tow strap 86 may be used tofacilitate wrapping the cuff around a nerve. The nerve cuff electrode 64includes electrode contacts 90A, 90B, 90C and 90D imbedded in the bodyof the cuff, with their inside surface facing exposed to establishelectrical contact with a nerve disposed therein. Electrode contacts 90Aand 90B are longitudinally and radially spaced from each other.Electrode contacts 90C and 90D are radially spaced from each other andpositioned longitudinally between electrode contacts 90A and 90B. Eachof the four electrode contacts may be operated independently via fourseparate conductors (four filar) in the lead body 62.

With specific reference to FIGS. 27B-27G, each includes a top view (leftside) to schematically illustrate the electrical field or activatingfunction (labeled E), and an end view (right side) to schematicallyillustrate the area of the nerve effectively stimulated (labeled S) andthe area of the nerve effectively not stimulated (labeled NS).Electrodes 90A-90D are labeled A-D for sake of simplicity only. Thepolarity of the electrodes is also indicated, with each of the cathodesdesignated with a negative sign (−) and each of the anodes designatedwith a positive sign (+).

With reference to FIG. 27B, a tripolar transverse guarded cathodearrangement is shown with electrodes C and D comprising cathodes andelectrodes A and B comprising anodes, thus stimulating the entirecross-section of the nerve.

With reference to FIG. 27C, a bipolar diagonal arrangement is shown withelectrode C comprising a cathode and electrode A comprising an anode,wherein the fascicles that are stimulated may comprise superiorfascicles of the hypoglossal nerve, and the fascicles that are notstimulated may comprise inferior fascicles of the hypoglossal nerve(e.g., fascicles that innervate the intrinsic muscles of the tongue).

With reference to FIG. 27D, another bipolar diagonal arrangement isshown with electrode D comprising a cathode and electrode B comprisingan anode, wherein the fascicles that are stimulated may compriseinferior fascicles of the hypoglossal nerve.

With reference to FIG. 27E, a bipolar axial arrangement is shown withelectrode A comprising a cathode and electrode B comprising an anode,wherein the fascicles that are stimulated may comprise lateral fasciclesof the hypoglossal nerve.

With reference to FIG. 27F, a bipolar transverse arrangement is shownwith electrode C comprising a cathode and electrode D comprising ananode, wherein the fascicles that are stimulated may comprise medialfascicles of the hypoglossal nerve.

With reference to FIG. 27G, a modified tripolar transverse guardedcathode arrangement is shown with electrode C comprising a cathode andelectrodes A and B comprising anodes, thus stimulating the entirecross-section of the nerve with the exception of the inferior medialfascicles.

Nerves like the hypoglossal nerve or superior laryngeal nerve typicallyinclude a plurality of fibers having relatively larger diameters and aplurality of fibers having relatively smaller diameters. In the case ofsingle function nerves, such as, for example, the hypoglossal nerve HGN,all of the nerve fibers may either be sensory or motor in function.However, in the case of multi-function nerves, such as, for example, thesuperior laryngeal nerve SLN, the fibers having relatively largerdiameters are typically motor (efferent) fibers, and the fibers havingrelatively smaller diameters are typically sensory (afferent) fibers.Accordingly, there may be a need to selectively stimulate the differingdiameter fibers in a nerve.

Turning now to FIG. 27H, there is depicted an embodiment of auni-directional stimulation electrode 2700 having a distal end 2700a anda proximal end 2700b. Electrode 2700 may include a substantiallycylindrical nerve cuff 2701 in accordance with the principles of thepresent disclosure. As illustrated, nerve cuff 2701 may include an outersurface 2701a and an inner surface 2701b. Electrode 2700 may furtherinclude a plurality of electrode contacts 2702-2704. Electrode contacts2702-2704 may be used as any suitable electrode contact known to thoseof ordinary skill in the art. For example, electrode contact 2702 may beused as an anode, electrode contact 2703 may be used as a cathode, andelectrode contact 2704 may be used as a second anode. Electrode contacts2702-2704 may also include any suitable shape and/or configuration knownin the art. For example, electrode contacts 2702-2704 may include asubstantially semi-circular configuration.

Electrode contacts 2702-2704 may be disposed on nerve cuff 2701 in anysuitable configuration to achieve the desired effect. For example,electrode contacts 2702-2704 may be disposed on inner surface 2701b. Asdepicted in FIG. 27H, cathode electrode contact 2703 may be disposedapproximately equidistant from distal end 2700a and proximal end 2700b,and anode electrode contacts 2702 may be differentially spaced aroundcathode electrode contact 2703, so as to control the direction ofstimulation of electrode 2700. For example, anode electrode contact 2702may be spaced from cathode electrode contact 2703 by any suitabledistance χ while second anode electrode contact 2704 may be spaced fromcathode electrode contact 2703 by a distance that is approximately twoor three times greater than distance χ. In this exemplary configuration,the direction of stimulation may be in the direction of arrow 2705.

In use, electrode 2700 may be implanted upon a nerve in accordance withthe principles of this disclosure. Electrode 2700 may be oriented on thenerve it is implanted on in any suitable manner, such as, for example,according to the direction of intended stimulation. Thus, incircumstances where it may be desired to stimulate efferent (motor)fibers of a nerve, such as, for example, the superior laryngeal nerveSLN, while avoiding stimulation to afferent (sensory) fibers of thenerve, the electrode 2700 may be oriented on the nerve in a manner suchthat anode electrode contact 2702 is located distally of cathodeelectrode contact 2703, with distal and proximal designations based onthe relative location of the electrode contact on the nerve.Alternatively, in circumstances where it may be desired to stimulateafferent fibers of a nerve while avoiding stimulation of efferent fibersof the nerve, the electrode 2700 may be oriented on the nerve in amanner such that anode electrode contact 2702 is located proximally ofcathode electrode contact 2703.

With reference now to FIG. 27I, there is depicted an embodiment of astimulation electrode 2750 for, among other things, selectivelystimulating differing diameter fibers of a nerve, such as, for example,the hypoglossal nerve or superior laryngeal nerve. Electrode 2750 mayinclude a body 2751, and may include any suitable configuration inaccordance with the principles of the present disclosure. Additionally,electrode 2750 may include an array 2752 of suitable electrode contactsknown to those skilled in the art. Although the depicted embodiment ofelectrode 2750 includes five electrode contacts 2753a-2753e, array 2752may include a greater or lesser number of electrode contacts. Electrodecontacts 2753a-2753e may be disposed on body 2751 in any suitableconfiguration to produce the desired effect. For example, as depicted inFIG. 27I, electrode contacts 2753a-2753e may be disposed serially, withapproximately a one (1) millimeter spacing in between each electrodecontact 2753a-2753e. Electrode contacts 2753a-2753e may be configured tofunction as either anode electrode contacts or cathode electrodecontacts, as desired.

Electrode contacts 2753 may be connected to an implanted neurostimulator(INS), such as, for example, INS 50, in accordance with the presentdisclosure. The INS may be programmed to select any of electrodecontacts 2753a-2753e for nerve stimulation. For example, incircumstances where it may be desired to stimulate the smaller diameterfibers of a nerve, it is contemplated that all electrode contacts2753a-2753e may be selected for nerve stimulation, since closely spacedelectrode contacts typically affect smaller diameter fibers (e.g.,afferent or sensory fibers). In these circumstances, electrode contacts2753a, 2753c, and 2753e may function as anode electrode contacts andelectrode contacts 2753b and 2753d may function as cathode electrodecontacts. In circumstances where it may be desired to stimulate thelarger diameter fibers of a nerve, it is contemplated that onlyelectrode contacts 2753a, 2753c, and 2753e may be selected for nervestimulation, since loosely spaced electrode contacts typically affectlarger diameter fibers (e.g., efferent or motor fibers). In thesecircumstances, electrode contacts 2753a and 2753e may function as anodeelectrode contacts, and 2753c may function as a cathode electrodecontact.

Alternatively, electrode 2750 may be utilized to reduce muscle fatiguewhen implanted on single function nerves, such as, for example, thehypoglossal nerve. In such circumstances, muscle fatigue may be reducedby alternatively switching between using loosely spaced electrodecontacts 2753a, 2753c, and 2753e, to stimulate large diameter fibers,and closely spaced electrode contacts 2753a-2753e, to stimulate smalldiameter fibers.

Turning to FIGS. 27J-27K, in accordance with the present disclosure,there is depicted another embodiment of a nerve cuff electrode 2760 forfacilitating reduction in muscle fatigue. Nerve cuff electrode 2760 mayinclude a body 2761 having a plurality of electrode contacts 2762, 2763,and 2764. Electrode contacts 2762-2764 may include any suitableelectrode contacts in accordance with the present disclosure. Althoughthe depicted embodiment of nerve cuff electrode 2760 includes threeelectrode contacts 2762-2764, nerve cuff electrode 2760 may include agreater or lesser number of electrode contacts. Furthermore, electrodecontacts may be disposed on body 2761 in any suitable configuration toachieve the desired effect, such as, for example, serially, as depicted.In the depicted embodiment, electrode contacts 2762 and 2764 mayfunction as anode electrode contacts, while electrode contact 2763 mayfunction as a cathode electrode contact. Electrode contact 2763 mayinclude two distinct, substantially triangularly shaped portions 2763aand 2763b. However, portions 2763a and 2763b may include any suitableshape. In addition, portions 2763a and 2763b may be configured to be ofdiffering conductive properties, so that, for the same stimulation pulse(e.g., a slow rising, small amplitude pulse having a relatively longduration of approximately 0.2 to 0.35 milliseconds) applied to each ofthe portions 2763a and 2763b, the resultant charge densities at thesurface of each of the portions 2763a and 2763b may be different. Forexample, portions 2763a and 2763b may be made of electrically differingmaterials. For discussion purposes only, it is assumed that portion2763a is configured to deliver a charge density lower than that ofportion 2763b. However, portion 2763a may be configured to deliver acharge density that is higher than the charge density of portion 2763b.

Since the small diameter fibers of a nerve are typically stimulated bylow charge densities and large diameter fibers of the nerve aretypically stimulated by high charge densities, portions 2763a and 2763bmay be sequentially utilized to alternate between stimulating the smalland large diameter fibers of a nerve. In other words, in use, astimulation pulse may be first delivered to portion 2763a to stimulatethe small diameter fibers of a nerve. A subsequent stimulation pulse maybe then delivered to portion 2763b to stimulate the large diameterfibers of a nerve. It is contemplated that alternating betweenstimulating the small and large diameter fibers of a nerve mayfacilitate reducing muscle fatigue while also ensuring sufficient musclemass is stimulated to maintain the necessary contraction and forcegeneration to successfully treat OSA.

Turning now to FIG. 27L, there is illustrated yet another embodiment ofa nerve cuff electrode 2780 for facilitating reduction in musclefatigue. For the purposes of this disclosure, nerve cuff electrode 2780may be substantially similar to nerve cuff electrode 2760. Nerve cuffelectrode 2780, however, may differ from nerve cuff electrode 2760 in atleast one significant way. For example, rather than having twosubstantially triangular portions, cathode electrode contact 2783 maycomprise two substantially different portions 2783a and 2783b. Portions2783a and 27836 may be spaced apart from one another and may includediffering surface areas. For example, as illustrated, portion 2783a mayinclude a smaller surface area than portion 2783b. Furthermore, portions2783a and 2783b may include any suitable shape known in the art.Although portions 2783a and 2783b in the illustrated embodiment togetherdefine a substantially triangular shaped electrode contact 2783,portions 2783a and 2783b together may or may not define any suitableshape known in the art.

Each of portions 2783a and 2783b may be configured to be substantiallysimilar in conductance despite their differing surface areas. Forexample, portion 2783a may be made of a first material having arelatively lower conductance, while portion 2783b may be made of asecond material having a relatively higher conductance. Thus, whensubjected to the same stimulation pulse (e.g., a slow rising, smallamplitude pulse having a relatively long duration of approximately 0.2to 0.35 milliseconds), portion 2783a may have a higher charge densitythan portion 2783b because of its relatively smaller surface area thanportion 2783b. Similarly, when subjected to the same stimulation pulse,portion 2783b may have a lower charge density than portion 2783a becauseof its relatively larger surface area than portion 2783a. Accordingly,because of the differing charge densities, portion 2783a may be adaptedto stimulate large diameter fibers of a nerve, and portion 2783b may beadapted to stimulate small diameter fibers of the nerve.

In use, a stimulation pulse may be first delivered to portion 2783a tostimulate the large diameter fibers of a nerve. A subsequent stimulationpulse may be then delivered to portion 2783b to stimulate the smalldiameter fibers of the nerve. It is contemplated that alternatingbetween stimulating the small and large diameter fibers of a nerve mayfacilitate muscle fatigue while also ensuring that sufficient musclemass is stimulated to maintain the necessary contraction and forcegeneration to successfully treat OSA.

In certain embodiments, such as when nerve cuff electrodes 2760 and 2780are implanted on a multi-function nerve (e.g., the superior laryngealnerve SLN), it is contemplated that portions 2763a/2763b and portions2783a/2783b may be utilized to selectively stimulate either the afferentor efferent fibers of the nerve.

With reference now to FIGS. 27M-27Q, there is depicted yet anotherembodiment of a nerve cuff electrode 2790 for minimizing muscle fatigue.Nerve cuff electrode 2790 may include a cuff body 2791 for mountingabout a nerve 2792 in accordance with the present disclosure. Cuff body2791 may include a plurality of electrode contacts 2793-2796 also inaccordance with the present disclosure. Although the depicted embodimentof nerve cuff electrode 2790 includes four electrode contacts 2793-2796,nerve cuff electrode 2790 may include a greater or lesser number ofelectrode contacts.

Nerve cuff electrode 2790 may be configured to selectively stimulateboth small diameter fibers contained in fascicle 2777a and largediameter fibers contained in fascicle 2777b of nerve 2792. For example,as shown in FIG. 27P, by applying an exemplary slow rising, long pulsewidth waveform to electrode contacts 2796 and 2793, nerve cuff electrode2790 may stimulate the small diameter fibers contained in fascicle 2777aof nerve 2792. Similarly, as shown in FIG. 27Q, by applying an exemplaryfast rising, short pulse width waveform to electrode contacts 2794 and2795, nerve cuff electrode 2790 may stimulate the large diameter fiberscontained in fascicle 2777b of nerve 2792. Fascicles 2777a and 2777b maybe stimulated simultaneously or separately. In embodiments, where it isdesirable to stimulate fibers contained in fascicles 2777a and 2777b,the pulse generator (e.g., INS 50) may be provided with dual outputports.

Description of Respiration Sensing Lead Anchoring Alternatives

With reference to the following figures, various additional oralternative anchoring features for the respiration sensing lead 70 areschematically illustrated. Anchoring the respiration sensing lead 70reduces motion artifact in the respiration signal and stabilizes thebio-impedance vector relative to the anatomy.

In each of the embodiments, by way of example, not limitation, therespiration sensing lead 70 includes a lead body 70 with a proximalconnector and a plurality of distal respiration sensors 74 comprisingring electrodes for sensing bio-impedance. The lead body 72 of therespiration sensing lead 70 may include a jacket cover containing aplurality of conductors 78, one for each ring electrode 74 requiringindependent control. Generally, the impedance electrodes 74 may comprisecurrent emitting electrodes and voltage sensing electrodes for detectingrespiration by changes in bio-impedance.

With reference to FIGS. 28-33, various fixation devices and methods areshown to acutely and/or chronically stabilize the respiratory sensinglead 70. With specific reference to FIG. 28, the INS 50 is shown in asubcutaneous pocket and the stimulation lead 60 is shown in asubcutaneous tunnel extending superiorly from the pocket. Therespiration sensing lead 70 is shown in a subcutaneous tunnelsuperficial to muscle fascia around the rib cage. A suture tab or ring270 may be formed with or otherwise connected to the distal end of thelead body 72. Near the distal end of the lead 70, a small surgicalincision may be formed to provide access to the suture tab 270 and themuscle fascia under the lead 70. The suture tab 270 allows the distalend of the lead 70 to be secured to the underlying muscle fascia bysuture or staple 272, for example, which may be dissolvable orpermanent. Both dissolvable and permanent sutures/staples provide foracute stability and fixation until the lead body 72 is encapsulated.Permanent sutures/staples provide for chronic stability and fixationbeyond what tissue encapsulation otherwise provides.

With reference to FIGS. 29A-29C, a fabric tab 280 may be used in placeof or in addition to suture tab 270. As seen in FIG. 29A, the fabric tab280 may be placed over a distal portion of the lead body 72, such asbetween two distal electrodes 74. A small surgical incision may beformed proximate the distal end of the lead 70 and the fabric tab 280may be placed over the over the lead body 72 and secured to theunderlying muscle fascia by suture or staple 282, for example, which maybe dissolvable or permanent, to provide acute and/or chronic stabilityand fixation. With reference to FIGS. 29B and 29C (cross-sectional viewtaken along line A-A), the fabric tab 280 may comprise a fabric layer(e.g., polyester) 284 to promote chronic tissue in-growth to the musclefascia and a smooth flexible outer layer (silicone or polyurethane) 286for acute connection by suture or staple 282.

With reference to FIG. 30, lead 70 includes a split ring 290 that may beformed with or otherwise connected to the distal end of the lead body72. The split ring 290 allows the distal end of the lead 70 to besecured to the underlying muscle fascia by suture or staple 292, forexample, which may be dissolvable or permanent. The ring 290 may beformed of compliant material (e.g., silicone or polyurethane) and mayinclude a slit 294 (normally closed) that allows the lead 70 to beexplanted by pulling the lead 70 and allowing the suture 292 to slipthrough the slit 294, or if used without a suture, to allow the ring todeform and slide through the tissue encapsulation. To further facilitateexplanation, a dissolvable fabric tab 282 may be used to acutelystabilize the lead 70 but allow chronic removal.

With reference to FIGS. 31A-31C, deployable anchor tines 300 may be usedto facilitate fixation of the lead 70. As seen in FIG. 31A, theself-expanding tines 300 may be molded integrally with the lead body 72or connected thereto by over-molding, for example. The tines 300 maycomprise relatively resilient soft material such as silicone orpolyurethane. The resilient tines 300 allow the lead 70 to be deliveredvia a tubular sheath or trocar 304 tunneled to the target sensing site,wherein the tines 300 assume a first collapsed delivery configurationand a second expanded deployed configuration. As seen in FIGS. 31B and31B′, the tubular sheath or trocar 301 may be initially tunneled to thetarget site using an obturator 306 with a blunt dissection tip 308.After the distal end of the tubular sheath 304 has been tunneled intoposition by blunt dissection using the obtruator 306, the obtruator 306may be removed proximally from the sheath 304 and the lead 70 withcollapsible tines 300 may be inserted therein. As seen in FIG. 31C, whenthe distal end of the lead 70 is in the desired position, the sheath 304may be proximally retracted to deploy the tines 300 to engage the musclefascia and adjacent subcutaneous tissue, thus anchoring the lead 70 inplace.

With reference to FIGS. 32A and 32B, an alternative deployable fixationembodiment is shown schematically. In this embodiment, self-expandingtines 310 are held in a collapsed configuration by retention wire 312disposed in the lumen of the lead body 72 as shown in FIG. 32A. Each ofthe tines 310 includes a hole 314 through which the retention wire 312passes to hold the tines 310 in a first collapsed delivery configurationas shown In FIG. 32A, and proximal withdrawal of the retention wire 314releases the resilient tines 310 to a second expanded deployedconfiguration as shown in FIG. 32B. The lead 70 may be tunneled to thedesired target site with the tines 310 in the collapsed configuration.Once in position, the wire 312 may be pulled proximally to release thetines 310 and secure the lead 70 to the underlying muscle fascia andadjacent subcutaneous tissue to establish fixation thereof.

With reference to FIGS. 33A and 33B, another alternative deployablefixation embodiment is shown schematically. In this embodiment,self-expanding structures such as one or more resilient protrusions 320and/or a resilient mesh 325 may be incorporated (either alone or incombination) into the distal end of the lead 70. By way of example, notlimitation, resilient protrusions 320 may comprise silicone orpolyurethane loops and resilient mesh 325 may comprise a polyesterfabric connected to or formed integrally with the lead body 72. Both theresilient protrusions 320 and the resilient mesh 325 may be delivered ina collapsed delivery configuration inside tubular sheath 304 as shown inFIG. 33A, and deployed at the desired target site by proximal retractionof the sheath 304 to release the self-expanding structures 320/325 to anexpanded deployed configuration as shown in FIG. 33B. Both the resilientprotrusions 320 and the resilient mesh 325 engage the underlying musclefascia through tissue encapsulation and adjacent subcutaneous tissues toprovide fixation of the lead 70 thereto.

Other fixation embodiments may be used as well. For example, thefixation element may engage the muscle fascia and adjacent subcutaneoustissues or may be embedded therein. To this end, the electrodes mayalternatively comprise intramuscular electrodes such as barbs or helicalscrews.

Description of Respiration Sensing Electrode Alternatives

A description of the various alternatives in number, spacing, anatomicallocation and function of the impedance electrodes follows. Generally, ineach of the following embodiments, the respiration sensing lead includesa lead body and a plurality of respiration sensors comprising ringelectrodes for sensing bio-impedance. The lead body may include aplurality of insulated conductors disposed therein, with one conductorprovided for each ring electrode requiring independent connection and/orcontrol. The impedance electrodes may comprise current emittingelectrodes and voltage sensing electrodes for detecting respiration bychanges in bio-impedance.

With reference to FIG. 34, the distal portion of a respiration sensinglead 70 is shown by way of example, not limitation. The respirationsensing lead 70 includes a lead body 72 with a proximal connector and aplurality of distal impedance electrodes 74. In this example, the leadbody 72 and electrodes 74 are cylindrical with a diameter of 0.050inches. The distal current-carrying electrode 74A may be 5 mm long andmay be separated from the voltage-sensing electrode 74B by 15 mm. Thedistal voltage sensing electrode may be 5 mm long and may be separatedfrom the proximal combination current-carrying voltage-sensing electrode74C by 100 mm. The proximal electrode 74C may be 10 mm long. Theproximal portion of the lead 70 is not shown, but would be connected tothe INS (not shown) as described previously. The lead body incorporatesa plurality of insulated electrical conductors (not shown), each ofwhich correspond to an electrode 74A-74C. The electrodes and conductorsmay be made of an alloy of platinum-iridium. The lead body 72 maycomprise a tubular extrusion of polyurethane, silicone, or a coextrusionof polyurethane over silicone. The conductors may be formed ofmulti-filar wire coiled to provide extensibility for comfort anddurability under high-cycle fatigue.

With reference to FIGS. 35A-35E, the position of the electrodes 74 maybe characterized in terms of bio-impedance or bio-Z vectors. The bio-Zvector may be defined by the locations of the voltage-sensing electrodes(labeled V₁ & V₂). The voltage-sensing electrodes may be located oneither side of the current-carrying electrodes (labeled I₁ & I₂). Forexample, it is possible to locate either one or both of thevoltage-sensing electrodes between the current-carrying electrodes asshown in FIG. 35A (4-wire configuration (I₁-V₁-V₂-I₂)), and it ispossible to locate either one or both of the current-carrying electrodesbetween the voltage-sensing electrodes as shown in FIG. 35B (inverted4-wire configuration (V₁-I₁-I₂-V₂)). While at least two separateelectrodes (I₁ & I₂) are required to carry current and at least twoseparate electrodes (V₁ & V₂) are required to measure voltage, it ispossible to combine the current carrying and voltage sensing functionsin a common electrode. Examples of combining voltage sensing and currentcarrying electrodes are shown in FIGS. 35C-35E. FIG. 35C (2-wireconfiguration (I₁ V₁-I₂V₂)) shows combination electrode I₁ V₁ and I₂ V₂where each of these electrodes is used to carry current and sensevoltage. FIG. 35D (3-wire configuration (I₁-V₁-I₂V₂)) and 35E (inverted3-wire configuration (V₁-I₁-I₂V₂)) show combination electrode I₂V₂ whichis used to carry current and sense voltage.

With reference to FIG. 36, insulative material such as strips 73 maycover one side of one or more electrodes 74A-74D to provide directionalcurrent-carrying and/or voltage-sensing. The insulative strips maycomprise a polymeric coating (e.g., adhesive) and may be arranged toface outward (toward the dermis) such that the exposed conductive sideof each electrode 74 faces inward (toward the muscle fascia and thoraciccavity). Other examples of directional electrodes would be substantiallytwo-dimensional electrodes such as discs or paddles which are conductiveon only one side. Another example of a directional electrode would be asubstantially cylindrical electrode which is held in a particularorientation by sutures or sutured wings. Another example of adirectional electrode would be an electrode on the face or header of theimplanted pulse generator. It would likely be desirable for the pulsegenerator to have a non-conductive surface surrounding the location ofthe electrode.

In addition to the cylindrical electrodes shown, other electrodeconfigurations are possible as well. For example, the electrodes may bebi-directional with one planar electrode surface separated from anotherplanar electrode surface by insulative material. Alternatively or incombination, circular hoop electrodes may be placed concentrically on aplanar insulative surface. To mitigate edge effects, each electrode maycomprise a center primary electrode with two secondary side electrodesseparated by resistive elements and arranged in series. An alternativeis to have each primary current-carrying electrode connected by aresistive element to a single secondary side electrode. The conductivehousing of the INS 50 may serve as an current-carrying electrode orvoltage-sensing electrode. Alternatively or in addition, an electrodemay be mounted to the housing of the INS 50.

Because bio-impedance has both a real and imaginary component, it ispossible to measure the bio-Z phase as well as magnitude. It may bepreferable to extract both magnitude and phase information from thebio-Z measurement because the movement of the lung-diaphragm-liverinterface causes a significant change in the phase angle of the measuredimpedance. This may be valuable because motion artifacts of other tissuehave less impact on the bio-Z phase angle than they do on the bio-Zmagnitude. This means the bio-Z phase angle is a relatively robustmeasure of diaphragm movement even during motion artifacts.

An example of a bio-Z signal source is a modulated constant-currentpulse train. The modulation may be such that it does not interfere withthe stimulation signal. For example, if the stimulation signal is 30 Hz,the bio-Z signal source signal may be modulated at 30 Hz or asub-multiple of 30 Hz such that bio-Z and stimulation do not occursimultaneously. The pulses in the pulse train may have a pulse widthbetween 1 uS to 1 mS, such as 100 uS. The pulses may be separated by aperiod of time roughly equal to the pulse width (i.e., on-time of thepulses). The number of pulses in a train may be determined by atrade-off between signal-to-noise and power consumption. For example, nomore than 10 pulses may be necessary in any given pulse train. Themagnitude of current delivered during the pulse on-time may be between10 uA and 500 uA, such as 50 uA.

Other wave forms of bio-Z source signal may be used, including, withoutlimitation, pulse, pulse train, bi-phasic pulse, bi-phasic pulse train,sinusoidal, sinusoidal w/ramping, square wave, and square w/ ramping.The bio-Z source signal may be constant current or non-constant current,such as a voltage source, for example. If a non-constant current sourceis used, the delivered current may be monitored to calculate theimpedance value. The current-carrying electrodes may have a singlecurrent source, a split-current source (one current source split betweentwo or more current-carrying electrodes), or a current mirror source(one current source that maintains set current levels to two or morecurrent-carrying electrodes). Different characteristics of the sensedsignal may be measured including, without limitation, magnitude, phaseshift of sensed voltage relative to the current source signal, andmulti-frequency magnitude and/or phase shift of the sensed signal.Multi-frequency information may be obtained by applying multiple signalsources at different frequencies or a single signal source whichcontains two or more frequency components. One example of a singlemultifrequency source signal is a square wave current pulse. Theresultant voltage waveform would contain the same frequency componentsas the square wave current pulse which would allow extraction of Bio-Zdata for more than a single frequency.

With reference to FIG. 37, the bio-Z vector may be oriented with regardto the anatomy in a number of different ways. For example, using theelectrode arrangement illustrated in FIG. 34 and the anatomicalillustration in FIG. 37, the bio-Z vector may be arranged such that theproximal combination electrode is located just to the right of and abovethe xiphoid below the pectoral muscle between the 5^(th) and 6^(th) ribsand the distal current-carrying electrode is located mid-lateral betweenthe 7^(th) and 8^(th) ribs, with the distal voltage-sensing electrodepositioned between the 6^(th) and 7^(th) ribs 10 mm proximal of thedistal current-carrying electrode. This arrangement places theelectrodes along the interface between the right lung, diaphragm andliver on the right side of the thoracic cavity. The lung-diaphragm-liverinterface moves relative to the bio-Z vector with every respiratorycycle. Because the lung has relatively high impedance when inflated andthe liver has relatively low impedance due to the conductivity of bloodtherein, this bio-Z vector arrangement across the lung-diaphragm-liverinterface provides for a strong respiratory signal that is indicative ofchanges between inspiration and expiration. In addition, because theheart is situated more on the left side, positioning the bio-Z vector onthe right side reduces cardiac artifact. The net result is a bio-Zvector that provides an excellent signal-to-noise ratio.

A variety of different bio-Z vector orientations relative to the anatomymay be employed. Generally, bio-Z vectors for monitoring respiration maybe located on the thorax. However, bio-Z electrodes located in the headand neck may also be used to define respiratory bio-Z vectors. By way ofexample, not limitation, the bio-Z vector may be arrangedtransthoracically (e.g., bilaterally across the thorax), anteriorly onthe thorax (e.g., bilaterally across the thoracic midline), across thelung-diaphragm-liver interface, perpendicular to intercostal muscles,between adjacent ribs, etc. A single bio-Z vector may be used, ormultiple independent vectors may be used, potentially necessitatingmultiple sensing leads. One or more bio-Z sub-vectors within a givenbio-Z vector may be used as well.

With reference to FIGS. 37A-37C, thoracic locations defining examples ofbio-Z vectors are shown schematically. FIG. 37A is a frontal view of thethorax, FIG. 37B is a right-side view of the thorax, and FIG. 37C is aleft-side view of the thorax. In each of FIGS. 37A-37C, the outline ofthe lungs and upper profile of the diaphragm are shown. As mentionedpreviously, a bio-Z vector may be defined by the locations of thevoltage-sensing electrodes. Thus, FIGS. 37A-37C show locations forvoltage sensing electrodes which would define the bio-Z vector.

There are several short bio-Z vectors which provide excellent signalscorrelated to diaphragmatic movement. In general, these vectors have atleast one end at or near the lower edge of the ribcage. The shortdiaphragmatic bio-Z vectors have been successfully used in canines invector lengths ranging from approximately less than ½ inch to a fewinches in length. FIG. 37A shows a variety of locations which arerepresentative of the locations which define such vectors. Locationsshown just below the ribcage on the person's right side are designatedas A, B, C, and D. Locations shown just below the ribcage on theperson's left side are E, F, G, and H. Locations shown just above thelower edge of the ribcage on the person's right side are I, J, K, and L.Locations shown just above the lower edge of the ribcage on the person'sleft side are M, N, P, and Q. The locations just above the lower edge ofthe ribcage would fall within a few inches of the lower edge. Shortdiaphragmatic monitoring vectors would be comprised of location pairswhich are relatively closely spaced. For example, vectors D-E, D-C, D-L,and D-K all provide good diaphragmatic signal. The possible vectors fallinto three groups. Exemplary vectors which measure primarilydiaphragmatic muscle contraction are A-B, B-C, C-D, D-E, E-F, F-G, andG-H. Exemplary vectors which measure a combination of diaphragmaticmuscle contraction combined with movement of the lung into the pleuralpocket as the diaphragm contracts are I-J, P-R, A-I, A-J, B-I, B-J, G-P,H-R, H-P, and G-R. Exemplary vectors which measure diaphragmatic musclecontraction combined with movement of the diaphragm away from thethoracic wall as that portion of the lung expands are J-K, K-L, M-N, andN-P. It is known that the signal from any given location may be affectedby body position and free vs. obstructed respiration. The respiratorysignal from short vectors at or near the lower edge of the ribcage maybe more robust (e.g., may be not be substantially affected) to bodyposition and obstructed respiration. A further means of obtaining asignal which may be also more robust to body position would be tomeasure the respiratory impedance from complimentary vectors and sum theresulting bio-Z measurements. Complimentary vectors would bemirror-images or nearly mirror images of one another. Examples ofvectors and their mirror images may be C-D and E-F, B-C and G-F, C-K andF-N.

By way of example, not limitation, the following bio-Z vectors may beeffective for monitoring respiration and/or for measuring artifacts forsubsequent removal of the artifact from the respiration signal. VectorC-G is across the upper left and upper right lobes of the lungs, andprovides a good signal of ribcage expansion with moderate cardiacartifact. Vector D-F is a short-path version of C-G that provides a goodrespiratory signature largely correlated with ribcage expansion, withless cardiac artifact than C-G, but may be sensitive to movement of armsdue to location on pectoral muscles. Vector C-D is a short-pathipsilateral vector of the upper right lung that may be sensitive to armmovement but has less cardiac artifact. Vector B-H is a transversevector of the thoracic cavity that captures the bulk of the lungs anddiaphragm movement. Vector B-H, however, may be relatively lesssusceptible to changes in body position, and may still provide agenerally good signal when the patient changes positions. In certaincircumstances, the signal produced by vector B-H may have a less thandesired signal to noise ratio. However, it is contemplated thatgenerally available methods of signal processing in accordance with thepresent disclosure may be utilized the improve signal to noise ratio ofthe signal produced by Vector B-H. Vector A-E is an ipsilateral vectoracross the lung-diaphragm-liver interface. Because the liver is higherin conductivity and has a different impedance phase angle than the lung,vector A-E1 yields a good signal on both bio-Z magnitude and phase withlimited cardiac artifact. Vector B-K is an ipsilateral vector across thelung-diaphragm-liver interface that is substantially between a commonset of ribs with a current path that is mostly perpendicular to theintercostal muscles. Because resistivity of muscle is much higherperpendicular to the muscle direction than parallel, vector B-K reducescurrent-shunting through the muscle which otherwise detracts from thesignal of the lung-diaphragm-liver interface. Vector A-K is anipsilateral vector across the lung-diaphragm-liver interface similar tovector A-E1 but is more sensitive to movement of thelung-diaphragm-liver interface than to changes in resistivity of thelung-diaphragm-liver interface due to inspired air volume and is thus agood indicator of diaphragm movement. Vector B-E1 is a vector across themiddle and lower right lung and is good for detecting diaphragm movementwith little cardiac artifact. Vector C-E1 is a vector across the upperand middle right lung and is also good for detecting diaphragm movementwith little cardiac artifact. Vector D-E1 is a vector across the upperright lung with little cardiac artifact. Vector A-D is an ipsilateralacross a substantial portion of the right lung and diaphragm with littlecardiac artifact, but may be susceptible to motion artifact due to armmovement. Vector E1-E2 is a vector across the heart and provides a goodcardiac signal that may be used for removing cardiac artifact from arespiratory signal. Vector E2-J is a vector across thelung-diaphragm-stomach interface that provides a good measure ofdiaphragm movement using bio-Z phase vs. magnitude because the stomachhas almost no capacitive component and generally low conductivity.Vector L-M is a trans-diaphragm vector that is generally across thelung-diaphragm-liver interface with little cardiac artifact. Vector L-Mmay be relatively less susceptible to body position and movement and mayyield a good signal even if the patient is laying on the side of thesensing lead. In embodiments where the signal produced by vector L-M hasa less than desired signal to noise ratio, it is contemplated thatgenerally available methods of signal processing may be utilized toimprove the signal to noise ratio of the signal produced by vector L-M.

Electrodes placed at any of the above-noted locations may include, butare not limited to, combination electrodes, such as, for example,electrodes capable of both providing a current charge and sensing avoltage.

With reference to FIGS. 37A and 38D, an exemplary vector selectionmethod 3800 for detecting and utilizing a signal from the vector thatproduces the most desirable signal of all vectors is discussed. Thedisclosed vector selection method 3800 may be performed continuously,periodically, singularly, and/or may be repeated as desired. Forexample, method 3800 may be performed once in a 24 hour period. Inaddition, one or more steps associated with method 3800 may beselectively omitted and/or the steps associated with method 3800 may beperformed in any order. The steps associated with method 3800 aredescribed in a particular sequence for exemplary purposes only.

With specific reference to FIG. 38D, method 3800 may include a pluralityof steps 3801-3803 for detecting and utilizing the signal with the bestcharacteristics of all signals produced by a plurality of vectors.Specifically, method 3800 may include sampling short distance vectorsfirst to determine if any of these vectors are producing a desirablesignal, step 3801. Method 3800 may also include sampling intermediatedistance vectors if the short distance vectors are not producing adesirable signal, step 3802. Method 3800 may further include samplinglong distance vectors if the intermediate distance vectors are notproducing a desirable signal, is step 3803.

Turning to FIG. 37A, there is depicted an exemplary embodiment of aneurostimulator in accordance with the principles of the presentdisclosure. The exemplary neurostimulator may include an implanted INS50 and implanted electrode contacts AA-DD. While the depicted embodimentincludes electrode contacts AA-DD disposed between a patient's 5^(th)and lowest ribs, electrode contacts AA-DD may be disposed at anysuitable location. Furthermore, electrode contacts AA-DD may include,but are not limited to, the combination electrodes discussed above. Inthe depicted embodiment, exemplary short distance vectors may includethe vectors between, for example, adjacent electrode contacts AA, BB,CC, and DD; exemplary intermediate distance vectors may include thevectors AA-CC, AA-DD, and BB-DD, and exemplary long distance vectors mayinclude the vectors between the INS 50 and each of electrode contactsAA-DD.

With reference to FIG. 37A and FIG. 38A, step 3801 may include, forexample, sampling short distance vectors AA-BB, BB-CC, and CC-DD firstto determine whether any of these vectors may be producing a sufficientsignal in accordance with the principles of this disclosure, since thesevectors generally produce signals with desirable signal to noise ratios.Next, step 3802 of method 3800 may include sampling the intermediatedistance vectors AA-CC, AA-DD, and BB-DD if the short distance vectorsare producing a less than desirable signal. Lastly, step 3803 of method3800 may include sampling the long distance vectors INS-AA, INS-BB,INS-CC, and INS-DD if the intermediate distance vectors are producing aless than desirable signal.

In some embodiments, it is contemplated that several short,intermediate, and long distance vectors may be continually sampled, evenif a desirable signal is being received from a short distance vector, inorder to identify secondary vector signals that may be utilized if thecurrently utilized vector signal fails for any reason. However, fullyprocessing the data from signals generated by all of the vectors mayrequire complex sensing circuitry and processing of detection algorithmsthat may utilize undesirable amounts of battery power. Therefore, it maybe desirable to only monitor selected characteristics of the secondaryvector signals. With specific reference to FIG. 38B, there is depictedan embodiment of a method 3850 for utilizing multiple sensing channelsto optimize respiratory sensing with minimal additional hardware andpower consumption. It uses a single sensing circuit which is timemultiplexed (interleaved) to sample each of the vectors. Since, as notedabove, fully processing the data from all vector signals may requirehigher computational power, method 3850 may be used to identify the bestvector signal for respiration detection, while simultaneously monitoringthe remaining vectors signals for only relevant fiducial points. Thesefiducial points may include, but are not limited to, significant“landmarks” within a signal, such as, for example, peak amplitude andtime, point of highest slew rate, and zero crossing. The detectedfiducial points for the secondary vector signals may be then stored in acircular buffer memory 3854 for analysis if the primary signal fails forany reason, thereby, allowing immediate switching to an alternate vectorsignal and eliminating the need for a long signal acquisition periodafter a need to switch vector signals has been determined.

In particular, method 3850 may include feeding the signals from allavailable vectors into a plurality of channel selection switches 3851.The signals may be then analyzed for relevant fiducials by therespiratory impedance sensing circuit 3853. Once relevant fiducials havebeen discriminated, it may be possible to identify the best vectorsignal for respiration signal analysis. The fiducials of the remainingvectors may be then stored in circular buffer memory 3854 (as notedabove) to facilitate switching to a secondary vector signal if theprimary signal is no longer suitable for respiration detection.

The periodic monitoring (or interleaving) of secondary vector signalsmay facilitate faster switching to those vector signals when necessary.In particular, it is contemplated that when a decision to switch to asecondary vector signal is made (i.e., when the primary signals degradesto a point where it is no loner desirable for detecting respiration),the saved data (e.g., relevant fiducials) may be used to “seed” a signalanalysis algorithm with recently collected data, so as to promote fastervector switching by eliminating the need to wait for collection ofsufficient data for the secondary vector signal. In other words, becauseselect information of a secondary signal is available before the signalis actually used for respiration detection, analysis of the secondarysignal for, among other things, respiration detection may begin slightlyfaster than it would have if no data was available.

Furthermore, in certain embodiments, additional impedance sensors may beused as backup sensors to the sensor generating the primary vectorsignal. In these embodiments, data from the secondary sensors may bealso analyzed to identify and save relevant fiducials in the memory.This stored information may be used to provide supplemental or alternateinformation to facilitate identifying appropriate respiratory timing,when switching vector signals becomes necessary as a result of primarysignal degradation.

The respiratory bio-Z signal is partly due to the resistivity changewhich occurs when air infuses lung tissue, partly due to the relativemovement of electrodes as the rib cage expands, and partly due to thedisplacement of other body fluids, tissue and organs as the lungs movealong with the ribcage and diaphragm. As described above, each vectormeasures certain of these changes to different extents. It may bedesirable, therefore, to combine vectors which have complementaryinformation or even redundant information to improve the respiratoryinformation of the bio-Z signal. To this end, multiple vectors may beused. For example, one vector may be used to sense changes in thelung-diaphragm-liver interface and a second vector may be used to detectchanges (e.g., expansion, contraction) of the lung(s). Examples of theformer include A-K, B-K, A-E1, B-E1, and A-B. Examples of the laterinclude D-F, B-D, C-G, D-E1, and C-E1. Note that some vectorcombinations which share a common vector endpoint such as A-E1, D-E1 andB-E1, B-D may use a common electrode which would simplify therespiratory sensing lead or leads.

An advantage of using the lung-diaphragm-liver interface vector is thatit provides a robust signal indicative of the movement of the diaphragmthroughout the respiratory cycle. The liver is almost two times moreelectrically conductive than lung tissue so a relatively large bio-Zsignal can be obtained by monitoring the movement of thelung-diaphragm-liver interface. Because the liver functions to filterall the blood in the body, the liver is nearly completely infused withblood. This helps to dampen out the cardiac artifact associated with thepulsatile flow of the circulatory system. Another advantage of thislocation is that vectors can be selected which avoid significant currentpath through the heart or major arteries which will help reduce cardiacartifact.

It is worth noting that diaphragm movement is not necessarilysynchronous with inspiration or expiration. Diaphragm movement typicallycauses and therefore precedes inspiration and expiration. Respiratorymechanics do allow for paradoxical motion of the ribcage and diaphragm,so diaphragm movement is not necessarily coincident with inspiration.During REM sleep, the diaphragm is the dominant respiratory driver andparadoxical motion of the ribs and diaphragm can be problematic,especially if movement of the ribcage is being relied upon as aninspiratory indicator. Monitoring the diaphragm for pre-inspiratorymovement becomes especially valuable under these circumstances. Bio-Zmonitoring of the diaphragm can be used as a more sophisticatedindicator of impending inspiration rather than the antiquated approachof desperately trying to identify and respond to inspiration inpseudo-real time based on sensors which are responding tocharacteristics of inspiration.

For purposes of monitoring respiration, it is desirable to minimizeshunting of the electrical current through tissues which are not ofinterest. Shunting may result in at least two problems: reduced signalfrom the lungs; and increased chance of artifacts from the shuntedcurrent path. Skeletal muscle has non-isotropic conductivity. Themuscle's transverse resistivity (1600 ohm-cm) is more than 5 times itslongitudinal resistivity (300 ohm-cm). In order to minimize the adverseeffect of shunting current, it is desirable to select bio-Z sensingvectors which are perpendicular to muscle structure if possible. Onesuch example is to locate two or more electrodes of a bio-Z sensingarray substantially aligned with the ribs because the intercostalmuscles are substantially perpendicular to the ribs.

Description of Respiration Signal Processing

With reference to FIG. 39, the neurostimulation system described hereinmay operate in a closed-loop process 400 wherein stimulation of thetargeted nerve may be delivered as a function of a sensed feedbackparameter (e.g., respiration). For example, stimulation of thehypoglossal nerve may be triggered to occur during the inspiratory phaseof respiration. Alternatively, the neurostimulation system describedherein may operate in an open-loop process wherein stimulation isdelivered as a function of preset conditions (e.g., historical averageof sleeping respiratory rate).

With continued reference to FIG. 39, the closed-loop process 400 mayinvolve a number of generalized steps to condition the sensed feedbackparameter (e.g., bio-Z) into a useable trigger signal for stimulation.For example, the closed-loop process 400 may include the initial step ofsensing respiration 350 using bio-Z, for example, and optionally sensingother parameters 360 indicative of respiration or other physiologicprocess. The sensed signal indicative of respiration (or otherparameter) may be signal processed 370 to derive a usable signal anddesired fiducials. A trigger algorithm 380, which will be discussed ingreater detail below, may then be applied to the processed signal tocontrol delivery of the stimulation signal 390.

As noted above, the present disclosure contemplates conditioning sensedbio-impedance into a useable trigger signal for stimulation. However,one exemplary limitation to using sensed bio-impedance may be the body'snominal impedance. In practice, a sensed bio-impedance signal may beobtained by applying a suitable, known current through one portion of atissue of interest and measuring the voltage potential across the sametissue. This measurement technique is illustrated in FIG. 38C and may bereferred to herein as the “direct measurement” technique. The appliedcurrent and measured voltage potentials may be used to calculate theimpedance of the tissue. It is this measured impedance that mayconstitute the sensed bio-impedance signal. However, sense bio-impedancesignals of the present disclosure have been found to typically includetwo components, a relatively large nominal body impedance component anda relatively small respiratory impedance component. Thus, since thebody's impedance constitutes a large portion of the sensed signal, itmay be difficult to detect that relatively small impedance changesassociated with respiration on top of a body's nominal impedance.Therefore, in accordance with the principles of the present disclosure,it may be desirable to “filter” the sensed impedance signal in a mannerso as to remove most or all of the body's nominal impedance, in order toimprove resolution of the respiratory signal. In some embodiments, thismay be achieved with the aid of a conventional Wheatstone bridge at ornear the front-end of an impedance measuring circuit. In particular, theWheatstone bridge may facilitate precise measurements of the relativelysmall impedance changes associated with respiration by removing most, ifnot all, of the body's nominal impedance.

Turning now to FIG. 39A, there is depicted an exemplary Wheatstonebridge 3900. The Wheatstone bridge 3900 may include an electricalcurrent source 3901. Wheatstone bridge 3900 may also include a firstresistor R₁ having an impedance Z₁ connected in series to a secondresistor R₂ having an impedance Z₂. Resistors R₁ and R₂ may be connectedin parallel to resistor R₃ having an impedance Z₃, which may beconnected serially to the patient's body having an impedance Z_(body).As discussed below, impedances Z₂ and Z₃ may be substantially similar toeach other. Wheatstone bridge 3900 may further include any suitablevoltage measuring device, such as, for example, those used inconjunction the direct measurement technique described above.

In use, the impedance Z₁ of exemplary bridge 3900 may be closely matchedto the expected impedance of a patient's body Z_(body), the impedance Z₂matched to impedance Z₃, and the voltage potential across voltagemeasuring device 3902 may be measured. It is contemplated that ifimpedances Z₁-Z₃ are closely matched to Z_(body), the measured voltagepotential across voltage measuring device 3902 will be predominantly dueto respiratory impedance changes and the voltage signal due to thebody's nominal impedance will be largely removed. Further, it iscontemplated that the voltage changes measured at 3902 due torespiratory impedance changes will have an amplitude that isapproximately ½ of the amplitude of the voltage changes, measured withthe above-noted direct-measurement technique, assuming the samecurrently flow through the body. The removal of the voltage signal dueto the body's nominal impedance while retaining ½ of the voltage signalamplitude due to changes in respiratory impedance, may facilitatedetecting the small impedance changes associated with respiration byimproving the resolution of those changes.

In other embodiments, the body's nominal impedance may be extracted andidentified (e.g., type, time, and value). be removed or reduced from asensed signal by, for example, introducing a nominal offset removalmodule 3921 into an impedance measuring circuit 3920 of the presentdisclosure, as depicted in FIG. 39B. An exemplary impedance-measuringcircuit may generally include feeding a sensed respiratory signal into ademodulator. The signal exiting the demodulator may be then fed into anintegrator, and the integrated signal exiting the integrator may then bedigitized for analysis. It is therefore contemplated that introducingnominal offset removal module 3921 to act upon the upon the signalexiting the demodulator may achieve the desired effect of removing orreducing the body's nominal impedance from a sensed impedance signal.

Turning now to FIG. 39C, module 3921 may include a switch S, a resistorR, a capacitor C, and a non-inverting amplifier A. The switch S,resistor R, and capacitor C create a sample and hold reference voltageto the difference amplifier A. The amplifier subtracts this referencevoltage from the input signal. The result is to remove or reduce thenominal body impedance component of the signal leaving mainly therespiratory component of the measured impedance. The Resistor-Capacitor(R-C) combination is selected such that it will track with changes innominal impedance levels but does not significantly distort therespiratory signal. Respiratory signal frequency components of interestare typically between 0.05 Hz and 3 Hz. There are several options forhow the Nominal Offset Removal may be operated. An implantedbio-impedance circuit would typically use a modulated excitation signalfor measuring impedance. In that case, the switch, S may be open whenthere is no signal present and may be closed whenever a signal ispresent. For example, if a Demodulator Signal is present for 1 ms every100 ms, switch S would be closed during all or a part of the time thatSignal In is present. Switch S may also be operated such that it doesnot close on every instance when Demodulator Signal is present. Theswitch S, may be closed on every 10^(th) or 100^(th) instance whenDemodulator Signal is present. A third possibility is to close switch Sonly when Signal Out causes the Integrator to reach an unacceptablethreshold. The integrator reaching an unacceptable threshold may beindicative that the reference voltage provided by the RC combination isno longer providing a sufficiently good estimate of the nominal signalcomponent and so needs to be updated with new information.

Turning now to FIG. 39D, there is depicted an alternative embodiment ofnominal offset removal module. A further improvement on the NominalOffset Removal module is shown in FIG. 39D. If it is desired to measuretwo or more different impedance signals it will be necessary to have adifferent nominal offset reference voltage provided to amplifier A foreach signal. It is also desirable to keep the component count as low aspossible. In the diagram below, S0 and S1 may be closed and S2 may beopen to provide an offset reference for a first signal with theappropriate combination of R-C1. S0 and S2 may be closed and S1 may beopen to provide an offset reference for a second signal with theappropriate combination of R-C2. This strategy allows rapid sequentialmeasurement of two or more impedance signals.

With reference to FIG. 40, the signal processing step 370 may includegeneral signal amplification and noise filtering 372. The step ofamplification and filtering 372 may include band pass filtering toremove DC offset, for example. The respiratory waveform may then beprocessed to remove specific noise artifacts 374 such as cardiac noise,motion noise, etc. A clean respiratory waveform may then be extracted376 along with other waveforms indicative of specific events such asobstructive sleep apnea (OSA), central sleep apnea (CSA), hypopnea,sleep stage, etc. Specific fiducial points may then be extracted andidentified (e.g., type, time, and value).

The step of removing specific noise artifacts 374 may be performed in anumber of different ways. However, before signal processing 374, bothcardiac and motion noise artifact may be mitigated. For example, bothcardiac and motion noise artifact may be mitigated prior to signalprocessing 374 by selection of bio-Z vectors that are less susceptibleto noise (motion and/or cardiac) as described previously. In addition,motion artifact may be mitigated before signal processing 374 byminimizing movement of the sensing lead and electrodes relative to thebody using anchoring techniques described elsewhere herein. Furthermore,motion artifact may be mitigated prior to signal processing 374 byminimizing relative movement between the current-carrying electrodes andthe voltage-sensing electrodes, such as by using combinedcurrent-carrying and voltage-sensing electrodes.

After cardiac and motion artifact has been mitigated using thepre-signal processing techniques described above, both cardiac andmotion artifact may be removed by signal processing 374.

For example, the signal processing step 374 may involve the use of a lowpass filter (e.g., less than 1 Hz) to remove cardiac frequency noisecomponents which typically occur at 0.5 to 2.0 Hz, whereas restingrespiration frequency typically occurs below 1.0 Hz.

Alternatively, the signal processing step 374 may involve the use of aband pass or high pass filter (e.g., greater than 1 Hz) to obtain acardiac sync signal to enable removal of the cardiac noise from thebio-Z signal in real time using an adaptive filter, for example.Adaptive filters enable removal of noise from a signal in real time, andan example of an adaptive filter is illustrated in FIG. 41. To removecardiac artifact from the bio-Z signal which contains both cardiac noisen(k) and respiratory information s(k), a signal n′(k) that representscardiac noise is input to the adaptive filter and the adaptive filteradjusts its coefficients to reduce the value of the difference betweeny(k) and d(k), removing the noise and resulting in a clean signal ine(k). Notice that in this application, the error signal actuallyconverges to the input data signal, rather than converging to zero.

Another signal processing technique to remove cardiac noise is tocombine signals from two or more bio-Z vectors wherein respiration isthe predominate signal with some cardiac noise. This may also be used toreduce motion artifact and other asynchronous noise. Each of the two ormore signals from different bio-Z vectors may be weighted prior tocombining them into a resultant signal Vw(i). If it is assumed that (a)the respiratory bio-impedance is the largest component in each measuredvector, (b) the non-respiratory signal components in one vector aresubstantially independent of the non-respiratory components in the othervector, and (c) the ratio of the non-respiratory component to therespiratory components in one vector is substantially equal to the sameratio in the other vector, then a simple weighting scheme may be usedwherein each signal is divided by it's historic peak-to-peak magnitudeand the results are added. For example, if M_(A)=historical averagepeak-to-peak magnitude of signal from vector A, M_(B)=historical averagepeak-to-peak magnitude of signal from vector B, V_(A)(i)=data point (i)from vector A, V_(B)(i)=data point (i) from vector B, then the resultantsignal V_(W)(i) (i.e., weighted average of A & B for data point (i)) maybe expressed as V_(W)(i)=V_(A)(i)/M_(A)+V_(B)(i)/M_(B).

Yet another signal processing technique for removing cardiac noise is tosubtract a first signal that is predominantly respiration from a secondsignal that is predominantly cardiac. For example, the first signal maybe from a predominantly respiratory bio-Z vector (e.g., vector B-H) withsome cardiac noise, and the second signal may be from a predominantlycardiac bio-Z vector (e.g., vector E1-E2) with some respiration signal.Each of the two signals from the different bio-Z vectors may be weightedprior to subtracting them. The appropriate weighting may be determined,for example, by calculating the power density spectra in the range of2-4 Hz for a range of weighted differences across at least severalrespiratory cycles. A minimum will occur in the power density spectrafor the weighted averages which are sufficiently optimal.

Motion artifact may be removed by signal processing 374 as well. Motionartifact may be identified and rejected using signal processingtechniques such as monitoring voltage magnitude, testing the correlationof magnitude and phase, and/or testing correlation at two or morefrequencies. Motion artifacts may cause a large change in measuredbio-impedance. A typical feature of motion artifacts is that the voltageswings are much larger than respiration. Another feature is that thevoltage changes are highly erratic. Using these characteristics, whichwill be described in more detail below, motion artifact may be removedfrom the respiration signal.

The step of extracting waveforms indicative of respiration and otherevents 374 may be better explained with reference to FIGS. 42-46 whichschematically illustrate various representative unfiltered bio-Zsignals. FIG. 42 schematically illustrates a bio-Z signal 420 withrepresentative signatures indicative normal respiration (i.e., eventfree) during an awake period 422 and a sleeping period 424. FIG. 43schematically illustrates a bio-Z signal 430 with representativesignatures indicative of normal respiration during sleeping periods 424interrupted by a period of motion 432 (i.e., motion artifact). FIG. 44schematically illustrates a bio-Z signal 440 with representativesignatures indicative of normal respiration during a sleeping period 424followed by periods of hypopnea (HYP) 442 and recovery 444. FIG. 45schematically illustrates a bio-Z signal 450 with representativesignatures indicative of normal respiration during a sleeping period 424followed by periods of obstructive sleep apnea (OSA) 452 and recovery454 (which typically includes an initial gasp 456). FIG. 46schematically illustrates a bio-Z signal 460 with representativesignatures indicative of normal respiration during a sleeping period 424followed by periods of central sleep apnea (CSA) 462 (which typicallyincludes a cessation in breathing 468) and recovery 464.

The step of extracting 374 waveform data indicative of an awake period422 vs. a sleep period 424 from a bio-Z signal 420 may be explained inmore detail with reference to FIG. 42. In addition, the step offiltering 372 waveform data indicative of motion 432 from a bio-Z signal430 may be explained in more detail with reference to FIG. 43. One wayto determine if a person is awake or moving is to monitor thecoefficient of variation (CV) of sequential peak-to-peak (PP) magnitudesover a given period of time. CV is calculated by taking the standarddeviation (or a similar measure of variation) of the difference betweensequential PP magnitudes and dividing it by the average (or a similarstatistic) of the PP magnitudes. N is the number of respiratory cycleswhich occur in the selected period of time.

The CV may be calculated as follows:

${CV} = \frac{{sd}({dPP})}{\overset{\_}{PP}}$

Where:

${{sd}({dPP})} = \sqrt{\frac{\sum\limits_{i = 1}^{N}\left( {{dPP}_{i} - \overset{\_}{dPP}} \right)}{\left( {N - 1} \right)}}$$\overset{\_}{dPP} = \frac{\sum\limits_{i = 1}^{N}\left( {dPP}_{i} \right)}{(N)}$dPP_(i) = PP_(i + 1) − PP_(i)$\overset{\_}{PP} = \frac{\sum\limits_{i = 1}^{N}\left( {PP}_{i} \right)}{(N)}$

Generally, if the CV is greater than 0.20 over a one minute period thenperson is awake. Also generally, if the CV is less than 0.20 over aone-minute period then person is asleep. These events may be flagged forthe step of fiducial extraction 378 wherein data (e.g., event duration,CV, PP range, PPmin, PPmax, etc.) may be time stamped and stored with anevent identifier. If CV is greater than 1.00 over a 20 second periodthen body movement is affecting the bio-Z signal. By way of example, notlimitation, if body movement is detected, then (a) stimulation may bedelivered in an open loop fashion (e.g., based on historical respiratorydata); (b) stimulation may be delivered constantly the same or lowerlevel; or (c) stimulation may be turned off during the period ofmovement. The selected stimulation response to detected movement may bepreset by the physician programmer or by the patient control device.Other stimulation responses may be employed as will be describedhereinafter.

In each of FIGS. 44-46, maximum and minimum peak-to-peak magnitudes(PPmax and PPmin) may be compared to distinguish hypopnea (HYP),obstructive sleep apnea (OSA), and central sleep apnea (CSA) events.Generally, PP values may be compared within a window defined by theevent (HYP, OSA, CSA) and the recovery period thereafter. Alsogenerally, the window in which PP values are taken excludes transitionalevents (e.g., gasp 456, 466). As a general alternative, peak-to-peakphases may be used instead of peak-to-peak magnitude. The hypopnea andapnea events may be flagged for the step of fiducial extraction 378wherein data (e.g., event duration, CV, PP range, PPmin, PPmax, etc.)may be time stamped and stored with an event identifier.

A typical indication of hypopnea (HYP) and apnea (OSA, CSA) events is arecurrent event followed by a recovery. The period (T) of each event(where PP oscillates between PPmax and PPmin and back to PPmax) may beabout 15 to 120 seconds, depending on the individual. The largest PPvalues observed during hypopneas and apneas are usually between 2 and 5times larger than those observed during regular breathing 424 duringsleep. The ratio of the PPmax to PPmin during recurrent hypopnea andapnea events is about 2 or more. During the event and recovery periods(excluding transitional events), PP values of adjacent respiratorycycles do not typically change abruptly and it is rare for the change inPP amplitude to be more than 50% of PPmax. One exception to thisobservation is that some people gasp 456, 466 (i.e., transitional event)as they recover from a CSA or OSA event.

The ratio of successive PP magnitudes during normal (non-event) sleep424 is mostly random. The ratio of successive PP magnitudes during apneaand hypopnea events will tend to be a non-random sequence due to theoscillatory pattern of the PP values. Recurrent apneas and hypopneas maybe diagnosed by applying a statistical test to the sequence ofsuccessive PP ratios.

The step of extracting 374 waveform data indicative of an hypopnea event442 from a bio-Z signal 440 may be explained in more detail withreference to FIG. 44. The ratio of PPmax to PPmin during recurrenthypopneas is typically between 2 and 5. This is in contrast to CSA'swhich have very small PPmin due to the complete cessation of breathing.This results in CSA's having PPmax to PPmin ratios larger than 5.Accordingly, hypopnea events may be detected, identified and flagged forthe step of fiducial extraction 378 wherein data (e.g., event duration,CV, PP range, PPmin, PPmax, etc.) may be time stamped and stored with anevent identifier.

The step of extracting 374 waveform data indicative of an OSA event 452from a bio-Z signal 450 may be explained in more detail with referenceto FIG. 45. The sharp change 456 in the bio-Z respiratory magnitude dueto OSA is typically in the range of 1 to 4 times the magnitude of thepeak-to-peak respiratory cycle magnitude. The sharp change 456 typicallytakes less than 5 seconds to occur. OSA tends to occur in a recurringsequence where the period (T) between sequential events is between 15and 120 seconds. A one-minute period is commonly observed. According tothese characteristics, OSA events may be detected, identified andflagged for the step of fiducial extraction 378 wherein data (e.g.,event duration, CV, PP range, PPmin, PPmax, etc.) may be time stampedand stored with an event identifier.

The step of extracting 374 waveform data indicative of a CSA event 462from a bio-Z signal 460 may be explained in more detail with referenceto FIG. 46. The behavior of the Bio-Z signal throughout recurrent CSAevents differ from other hypopnea and OSA in three ways. First, duringCSA there is complete cessation of respiratory activity which results ina flat Bio-Z signal. This means the ratio of PPmax to PPmin is typicallygreater than 5 during recurrent CSA events. The duration of theestimated respiratory cycle may also be used to distinguish between CSAfrom OSA and hypopnea. The lack of respiratory activity during CSAresults in an inflated estimate for the respiratory cycle period. The PPtypically does not vary by more than 50% for successive cycles. Therespiratory cycle duration during a CSA event is more than twice as longas the duration of the respiratory cycles preceding the CSA event.Second, during CSA the Bio-Z magnitude will drift outside the PPmagnitude range observed during respiration. It has been observed thatwith the onset of central sleep apnea (CSA) the magnitude and phase ofthe Bio-Z signal settle to a steady-state value outside the peak-to-peakrange observed during the normal respiratory cycle during sleep. Third,upon arousal from CSA a person will typically gasp. This gasp results ina large PP. The PP of the first respiratory cycle following the CSAevent and the PP observed during the CSA (which is essentially noise)will exceed 50% of PPmax.

With continued reference to FIG. 6, the flat portions 468 of the datatraces are periods of respiratory cessation. Upon arousal the subjectgasps 466 and the raw bio-Z signal resumes cyclic oscillation above thestatic impedance level observed during CSA. According to thesecharacteristics, CSA events may be detected, identified and flagged forthe step of fiducial extraction 378 wherein data (e.g., event duration,CV, PP range, PPmin, PPmax, etc.) may be time stamped and stored with anevent identifier.

The step of extracting 374 waveform data indicative of sleep stage(e.g., rapid eye movement (REM) sleep vs. no-rapid eye movement (NREM)sleep) may be performed by comparing the phase difference between afirst vector and a second vector wherein the first bio-Z vector is alongthe lung-diaphragm-liver interface (e.g., vector A-K or vector B-K) andthe second bio-Z vector is about the lung(s). Examples of the firstbio-Z vector include A-K, B-K, A-E1, B-E1, and A-B. Examples of thesecond bio-Z vector include D-F, B-D, C-G, D-E1, and C-E1. Note thatsome vector combinations which share a common vector endpoint such asA-E1, D-E1 and B-E1, B-D may use a common electrode and to simplify therespiratory sensing lead or leads. Typically, during NREM sleep, the twovectors are substantially in phase. During REM sleep, the diaphragm isthe primary respiratory driver and a common consequence is paradoxicalmotion of the ribcage and diaphragm (i.e., the two vectors aresubstantially out of phase). This characteristic would allow for aneffective monitor of a person's ability to reach REM sleep. Accordingly,REM and NREM sleep stages may be detected, identified, and flagged forthe step of fiducial extraction 378 wherein characteristic data (e.g.,event duration, phase, etc.) may be time stamped and stored with anevent identifier.

An alternative method of detecting an OSA event is to make use of asplit current electrode arrangement as shown in FIG. 47 which shows thepositions of three electrodes on the subject. Electrode A may be abovethe zyphoid, electrode B may be just above the belly button, andelectrode C may be on the back a couple of inches below electrode A.Electrodes A and B are connected to a common constant current sourcethrough resistors R1 and R2. The voltage measured across the currentsource is a measure of the bio-impedance during normal respiration. Thevoltage across R1 is an indicator of the paradoxical motion associatedwith apnea. An unbalanced current split between R1 and R2 resulting inlarge bio-Z voltage swings is indicative of OSA. During normalrespiration or even very deep breaths there is almost no effect on theapnea detection channel. Accordingly, OSA events may be detected,identified, and flagged for the step of fiducial extraction 378 whereincharacteristic data (e.g., event duration, voltage swing magnitude,etc.) may be time stamped and stored with an event identifier.

Generally, the extracted 378 waveform and event data may be used fortherapy tracking, for stimulus titration, and/or for closed loop therapycontrol. For example, data indicative of apneas and hypopneas (or otherevents) may be stored by the INS 50 and/or telemetered to the patientcontrolled 40. The data may be subsequently transmitted or downloaded tothe physician programmer 30. The data may be used to determinetherapeutic efficacy (e.g., apnea hypopnea index, amount of REM sleep,etc.) and/or to titrate stimulus parameters using the physicianprogrammer 30. The data may also be used to control stimulus in a closedloop fashion by, for example, increasing stimulus intensity duringperiods of increased apnea and hypopnea occurrence or decreasingstimulus intensity during periods of decreased apnea and hypopneaoccurrence (which may be observed if a muscle conditioning effect isseen with chronic use). Further, the data may be used to turn stimuluson (e.g., when apnea or hypopnea events start occurring or when motionartifact is absent) or to turn stimulus off (e.g., when no apnea orhypopnea events are occurring over a present time period or when motionartifact is predominant).

Description of Stimulus Trigger Algorithms

As mentioned previously with reference to FIG. 39, the neurostimulationsystem described herein may operate in a closed-loop process wherein thestep of delivering stimulation 390 to the targeted nerve may be afunction of a sensed feedback parameter (e.g., respiration). Forexample, stimulation of the hypoglossal nerve may be triggered to occurduring the inspiratory phase of respiration. In a health human subject,the hypoglossal nerve is triggered about 300 mS before inspiration.Accordingly, a predictive algorithm may be used to predict theinspiratory phase and deliver stimulation accordingly. FIG. 48schematically illustrates a system 480 including devices, data andprocesses for implementing a self-adjusting predictive triggeralgorithm.

The system components 482 involved in implementing the algorithm mayinclude the physician programmer (or patient controller), INS andassociated device memory, and the respiratory sensor(s). The sensors anddevice memory are the sources of real-time data and historical fiducialdata which the current algorithm uses to generate a stimulation triggersignal. The data 484 utilized in implementing the algorithm may includepatient specific data derived from a sleep study (i.e., PSG data), datafrom titrating the system post implantation, and historic and real-timerespiratory data including respiratory and event fiducials. Theprocesses 486 utilized in implementing the algorithm may includeproviding a default algorithm pre-programmed in the INS, patientcontroller or physician programmer, modifying the default algorithm, andderiving a current algorithm used to generate a trigger signal 488.

More specifically, the processes 486 utilized in implementing apredictive trigger algorithm may involve several substeps. First, adefault algorithm may be provided to predict onset of inspiration fromfiducial data. Selecting an appropriate default algorithm may depend onidentifying the simplest and most robust fiducial data subsets whichallow effective prediction of onset. It also may depend on a reliablemeans of modifying the algorithm for optimal performance. Second,modification of the default algorithm may require a reference datum. Thereference datum may be the estimated onset for past respiratory cycles.It is therefore useful to precisely estimate inspiratory onset forprevious respiratory cycles from historical fiducial data. Thisestimation of inspiratory onset for previous respiratory cycles may bespecific to person, sensor location, sleep stage, sleep position, or avariety of other factors. Third, the current algorithm may be derivedfrom real-time and historical data to yield a stimulation trigger signal488.

As alluded to above, a trigger algorithm, such as, for example, triggeralgorithm 4700 depicted in FIG. 47A, may be applied to a detectedrespiratory signal to begin and/or control delivery of the stimulationsignal. As illustrated, trigger algorithm 4700 may include a pluralityof sub-routines 4701-4703 for performing various analyses on a sensedrespiratory signal. These sub-routines may include, but are not limitedto, performing peak detection 4701, error checking 4702, and prediction4703, on a detected respiratory signal.

With reference now to FIG. 47D, there is depicted an exemplary sensedrespiratory signal 4750. Respiratory signal 4750 may be displayed as asubstantially sinusoidal waveform having a component that varies withtime. As shown in FIG. 47D, respiratory signal 4750 may include aplurality of peaks, such as, for example, the peak located at v₄t₄, anda plurality of valleys, such as, for example, the valley located v−₄t−₄.Therefore, as will be discussed in greater detail below, peak detectionsub-routine 4701 may be applied to sensed respiratory signal 4750 todetect the peaks of signal 4750. Error checking sub-routine 4702 may beapplied to signal 4750 to, among other things, ensure signal 4750 is anaccurate representation of a patient's respiration and free fromundesirable artifacts caused by, for example, a patient's movement orcardiac activity. Prediction sub-routine 4703 may then be applied tosignal 4750 to predict when future peaks will occur in accordance withthe sensed signal 4750.

With reference to FIG. 47B, peak detection 4701 may include a pluralityof steps 4701a-g. Step 4701a may include first detecting the peaks, suchas, for example, the peak located at v₄t₄, of signal 4750. The detectedpeaks may be an indication of when onset of expiration occurs during themonitored respiratory cycles. Next, step 4701b may include acquiringand/or considering a new voltage V_(k), where V_(k) may be the mostrecently acquired data point time T_(k) under consideration, where anumber of recently acquired data points may be under consideration. Step4701c may determine whether the data points under consideration meet thecriteria to indicate that a minimum (min) peak has been detected. Oneexample of such a criteria to indicate a minimum peak has been detectedis if the oldest data point under consideration, V_(k+m) is less thanmore recent data points under consideration, (V_(k+m−1) . . . V_(k)),which can be expressed mathematically as V_(k+m)≤min (V_(k+m−1) . . .V_(k)). Another example of such a criteria to indicate a minimum peakhas been detected is if the most recent data point under consideration,V_(k), is greater than all other less-recently acquired data pointsunder consideration, (V_(k+m) . . . V_(k+1)), which can be expressedmathematically as V_(k)≥max (V_(k+m) . . . V_(k+1)). If the criteria fordetecting a minimum peak is not met, step 4701b may be repeated toacquire and/or consider a new voltage V_(k). If the criteria has beenmet, step 4701d may declare a minimum peak reference. Next, step 4701emay again acquire and/or consider a new voltage V_(k). Subsequently,step 4701f may determine whether the data points under considerationmeet the criteria to indicate a maximum peak has been detected. Oneexample of such a criteria to indicate a maximum peak has been detectedis if the oldest data point under consideration, V_(k+m), is greaterthan more recent data points under consideration (V_(k+m−1) . . .V_(k)), which can be expressed mathematically as V_(k+m)≥max (V_(k+m−1). . . V_(k)). Another example of such a criteria to indicate a maximumpeak has been detected is if the most recent data point underconsideration, V_(k), is less than all other less-recently acquired datapoints under consideration, (V_(k+m) . . . V_(k+1)), which can beexpressed mathematically as V_(k)≥max (V_(k+m) . . . V_(k+1)). If thecriteria for detecting a maximum peak is not met, step 4701e may berepeated to acquire and/or consider a new voltage V_(k). If the criteriahas been met, step 4701g may declare a maximum peak, and triggeralgorithm 4700 may proceed to error-checking sub-routine 4702. Thedeclared peak will depend on the criteria used for peak detection. Forexample, if the criteria for detecting a peak was based on comparingV_(k) to less recently acquired data points, (V_(k+m) . . . V_(k+1)),then the peak magnitude and time would be declared to be V_(k+m/2),t_(k+m/2). As another example, if the criteria for detecting a peak wasbased on comparing the oldest considered data point, V_(k+m), to morerecently acquired data points (V_(k+m−1) . . . V_(k)), then the peakmagnitude and time would be declared to be V_(k+m), t_(k+m).

With reference now to FIG. 47C, error-checking sub-routine 4702 mayinclude a plurality of steps 4702a-e to determine whether a sensedrespiratory signal may be adequate for respiration detection. Forexample, step 4702a, peak correction, may include receiving informationrelating to the peaks detected in step 4701 and corrections, asnecessary. Next, steps 4702b-e may include analyzing the sensedrespiratory signal to determine whether the signal includes “noise”caused by a patient's movement (4702b), whether the signal issub-threshold (e.g., has a relatively low amplitude) (4702c), whetherthe signal is sufficiently stable (4702d), and whether the inversiondetection is possible with the sensed signal (4702e). If the sensedsignal passes all of error-checking steps 4702b-e, trigger algorithm4700 may proceed to prediction sub-routine 4703. However, if the sensedsignal fails any of steps 4702b-e, the trigger algorithm may terminateand the pulse generator (e.g., INS 50) may either cease stimulation,continue stimulation with continuous pulses of predetermined duration,and/or continue to stimulate at the same or a fraction (e.g., onequarter) of the stimulation rate for the most recently measuredrespiratory cycle, as discussed in greater detail below.

As described above, a peak is declared for a given set of data pointsunder consideration when a peak detection criteria is met. The declaredpeak itself may be used in further algorithm calculations or a moreprecise estimate of peak time and voltage may be calculated. The moreprecise estimates of peak time and voltage are referred to as the peakcorrection. With regard to step 4702a, peak correction may be calculatedas follows:ΔV_(pk,i)=V_(pk,j)−V_(pk,i−1) for −n≤i≤nV_(pk,0) is defined to be the declared peak for which a correction isbeing calculated. The difference in voltage between successive datapoints is calculated for a given number of data points, n, to eitherside of the declared peak.

${\Delta\; V_{{pk},{0{th}}}} = {\frac{1}{2n}{\Sigma\left( {\Delta\; V_{{pk},i}} \right)}}$The peak in signal ideally occurs when the rate of change of the signalis zero. Taking successive differences in measured voltage is anapproximation to the rate of change of the signal. Linear regression isused on a range of successive differences to estimate the point in timewhen the rate of change is zero. Due to the fact that the data pointsare collected at equal increments of time, calculating the statisticsΔV_(pk,0th), ΔV_(pk,1st) and DEN allows a simple calculation based onlinear regression to estimate the point in time at which the rate ofchange of the signal is zero.

Δ V_(pk, 1st) = Σ(i * Δ V_(pk, i))  for   − n ≤ i < nDEN = Σ(i²)  for   − n ≤ i ≤ n${Correction} = {\Delta\;{V_{{pk},{0{th}}}\left( \frac{DEN}{\Delta\; V_{{pk},{1{st}}}} \right)}}$Additionally, an estimated peak time after correction may be determinedas follows:t′_(pk,0)=t_(pk,0)+Correction

With regards to step 4702e, a peak curvature estimate for inversiondetection can be obtained from one of the statistics, ΔV_(pk,1st),calculated for peak correction. Maximum peaks are sharper than minimumpeaks and so typically have higher values of ΔV_(pk,1st). One means ofdetermining if a signal is inverted would be to compare the values ofΔV_(pk,1st) for a series of maximum peaks to a series of minimum peaks.

With renewed reference to FIG. 47A, prediction sub-routine 4703 mayinclude predicting the time between sequentially identified peaks witheither a parametric option or a non-parametric option. The parametricoption makes a prediction of the duration of the next respiratory periodbased on the average duration of recent respiratory cycles and the rateof change of the duration of recent respiratory cycles. The parametricoption also takes advantage of the fact that data points are collectedat equal increments of time which simplifies the linear regressioncalculation. The parametric option may be defined as follows:Δt_(i)=t_(i)−t_(i−1)

Zeroth order estimate of next peak.

Δ t_(0, 0th) = 1/h ⋅ Σ(Δ t_(i)), for  1 ≤ i ≤ n

where n is the number of past respiration cycles used

First Order Estimate

${{\Delta\; t_{0,{1{st}}}} = {\Sigma\left( {i - {\left( \frac{n + 1}{2} \right)*\Delta\; t_{i}}} \right)}},{{{for}\mspace{14mu} 1} \leq i \leq n}$${{{DEN}\; 1} = {\Sigma\left( \left( {i - \left( \frac{n + 1}{2} \right)} \right)^{2} \right)}},{{{for}\mspace{14mu} 1} \leq i \leq n}$

Predicted Interval Length for Current Respiration Cycle

${\Delta\; t_{0,{pred}}} = {{\Delta\; t_{0,{0{th}}}} + {\left( \frac{\Delta\; t_{0,{1{st}}}}{{DEN}\; 1} \right) \cdot \left( \frac{n + 1}{2} \right)}}$

Next Predicted Offset att_(0,pred)=t_(i)+Δt_(0,pred)

Begin therapy delivery at:t_(therapy)=t₁+(1−DC)*Δt_(0,pred), where DC may be the allowable dutycycle for therapy delivery.

The non-parametric option is very similar to the parametric option inthat it also estimates the duration of the next respiratory period basedon the nominal duration of recent respiratory cycles and the rate ofchange of the duration of recent respiratory periods. The method isexplained in more detail in “Nonparametric Statistic Method” byHollander and Wolfe in sections related to the Theil statistic and theHodges-Lehman, there disclose of which is incorporated herein byreference. The non-parametric prediction method may be defined asfollows:Δt_(i)=t_(i)−t_(i−1)

Zeroth Order EstimateΔt_(0,oth)=½ median{Δt_(i)+Δt_(j), i+∈₀≤j≤1, . . . , n}

Where ∈₀ is optimally 0, 1, 2 or 3

First Order Estimate

$S_{ij} = {{{\frac{{\Delta\; t_{j}} - {\Delta\; t_{i}}}{j - i}1} \leq {i +}} \in_{1}{< j \leq n}}$

where ∈₁ is optimally 0, 1, 2, or 3Δt_(0,1st)=median{S_(ij), 1≤i≤∈₁<j≤n}

Predicted Interval Length for Current Respiration cycle

${\Delta\; t_{0,{pred}}} = {{\Delta\; t_{0,{0{th}}}} + {\Delta\;{t_{0,{1{st}}} \cdot \left( \frac{n + 1}{2} \right)}}}$

Next Predicted Offsett_(0,pred)=t₁+Δt_(0,pred)

Begin Therapy Delivery att_(therapy)=t₁+(1−DC))*Δt_(0,pred), where DC may be the allowable dutycycle for therapy delivery.

Stimulation may then commence at the calculated t_(therapy).

With reference to FIG. 48, a self adjusting predictive algorithm may beimplemented in the following manner.

The Programmer block illustrates means by which PSG-derived data may beuploaded into the device.

The Sensors and Device Memory block includes the sources of real-timedata and historical fiducial variables which the current algorithm usesto generate a stimulation trigger signal.

The Patient PSG Titration Data block includes conventionalpolysomnographic (PSG) data obtained in a sleep study. A self-adjustingpredictive algorithm utilizes a reference datum to which the algorithmcan be adjusted: Onset may be defined as onset of inspiration asmeasured by airflow or pressure sensor used in a sleep study, forexample. Estimated Onset may be defined as an estimate of Onsetcalculated solely from information available from the device sensors andmemory. To enable the predictive algorithm to be self-adjusting, eitherOnset or Estimated Onset data is used. During actual use, the implanteddevice will typically not have access to Onset as that would requireoutput from an airflow sensor. The device then may rely on an estimateof Onset or Estimated Onset. The calibration of Estimated Onset to Onsetmay be based on PSG data collected during a sleep study. The calibrationmay be unique to a person and/or sleep stage and/or sleep positionand/or respiratory pattern.

The Historical Fiducial Variables block represents the HistoricalFiducial Variables (or data) which have been extracted from the bio-Zwaveform and stored in the device memory. This block assumes that theraw sensor data has been processed and is either clean or has beenflagged for cardiac, movement, apnea or other artifacts. Note thatfiducial data includes fiducials, mathematical combinations of fiducialsor a function of one or more fiducials such as a fuzzy logic decisionmatrix.

The Real-Time Data and Historical Fiducial Variables block incorporatesall the information content of the Historical Fiducial Variables blockand also includes real-time bio-Z data.

The Default Algorithm block represents one or more preset triggeralgorithms pre-programmed into the INS or physician programmer. Thedefault algorithm used at a specific point in time while deliveringtherapy may be selected from a library of pre-set algorithms. Theselection of the algorithm can be made automatically by the INS basedon: patient sleep position (position sensor), heart rate (detectablethrough the impedance measuring system) or respiration rate. Clinicalevidence supports that the algorithm used to predict the onset ofinspiration may be dependant on sleep position, sleep state or otherdetectable conditions of the patient.

The Modify Algorithm block represents the process of modifying theDefault Algorithm based on historical data to yield the CurrentAlgorithm. Once the calibration of Estimated Onset to Onset is residentin the device memory it can be used to calculate Estimated Onset forpast respiratory cycles from Fiducial Variables. The variable used torepresent the Estimated Onset will be TEST or TEST(i) where the “i”indicates the cycle number. Note that Estimated Onset is calculated forpast respiratory cycles. This means that sensor fiducial variables whicheither proceed or follow each Onset event may be used to calculate theEstimated Onset.

The Current Algorithm block represents the process of using the ModifiedDefault Algorithm to predict the next inspiratory onset (PredictedOnset). The Predicted Onset for the next respiratory cycle may becalculated from real-time data and historical fiducial variables. Thecalculation may be based on the Modified Default Algorithm. Modificationof the Modified Default Algorithm to derive the Current Algorithm may bedependent on the calibration of Estimated Onset to Onset which was inputfrom the physician programmer and may be based on comparison ofreal-time bio-Z data to data collected during a PSG titration study. TheCurrent Algorithm may use historic and/or real-time sensor fiducialvariables to predict the next onset of inspiration. This predicted onsetof inspiration may be referred to as Predicted Onset. The variable usedto represent Predicted Onset may be TPRED or TPRED(i) where the “i”indicates the respiratory cycle.

The Stimulation Trigger Signal block represents the Current Algorithmgenerating a trigger signal which the device uses to trigger stimulationto the hypoglossal nerve.

FIG. 49 is a table of some (not all) examples of waveform fiducialswhich can be extracted from each respiratory cycle waveform. For eachfiducial there is a magnitude value and a time of occurrence. Eachwaveform has a set of fiducials associated with it. As a result,fiducials may be stored in the device memory for any reasonable numberof past respiratory cycles. The values from past respiratory cycleswhich are stored in device memory are referred to as Historical FiducialVariables.

The graphs illustrated in FIG. 50 are examples of fiducials marked onbio-Z waveforms. The first of the three graphs illustrate thebio-impedance signal after it has been filtered and cleared of cardiacand motion artifacts. The first graph will be referred to as the primarysignal. The second graph is the first derivative of the primary signaland the third graph is the second derivative of the primary signal. Eachgraph also displays a square wave signal which is derived from airflowpressure. The square wave is low during inspiration. The falling edge ofthe square wave is onset of inspiration.

Due to the fact that it may be difficult to identify onset ofinspiration in real-time from respiratory bio-impedance, a goal is toconstruct an algorithm which can reliably predict onset of inspiration“T” for the next respiratory cycle from information available from thecurrent and/or previous cycles. A reliable, distinct and known referencepoint occurring prior to onset of inspiration, “T”, is “A”, the peak ofthe primary signal in the current cycle. As can be seen in FIG. 50, theupper peak of the bio-Z waveform “A” approximately corresponds to theonset of expiration “O.” A dependent variable t_(T−PK) is created torepresent the period of time between the positive peak of the primarysignal for the current cycle, t·Vmax(n), indicated by “A_(n)” on thegraph, and onset of inspiration for the next cycle, t·onset(n+1),indicated by “T” on the graph. The variable t_(T−PK) may be defined as:t_(T−PK)=t·onset(n+1)−t·Vmax(n)

Note that t·Vmax could be replaced by any other suitable fiducial indefining a dependent variable for predicting onset.

A general model for a predictive algorithm may be of the following form:

t_(T−PK)=f(fiducials extracted from current and/or previous cycles)

A less general model would be to use a function which is a linearcombination of Fiducial Variables and Real-Time Data.

The following fiducials may be both highly statistically significant andpractically significant in estimating T:t·Vmax(n)=the time where positive peak occurs for the current cycle;t·dV·in(n)≈the time of most positive 1^(st) derivative duringinspiration for the current cycle; andt·Vmax(n−1)=the time of positive peak for the previous cycle.

This model can be further simplified by combining the variables asfollows:Δt·pk(n)=t·Vmax(n)−t·Vmax(n−1)Δt·in(n)=t·Vmax(n)−t·dV·in(n)

Either Δt·pk(n) or Δt·in(n) is a good predictor of Onset.

The following example uses Δt·pk(n). The time from a positive peak untilthe next inspiration onset can be estimated by:T_(pred)=t·Vmax(n)+k0+k1*Δt·pk(n)

The coefficients k0 and k1 would be constantly modified by optimizingthe following equation for recent historical respiratory cycles againstT_(est):T_(est)≈t·Vmax(n)+k0+k1*Δt·pk(n)

Thus, the predictive trigger time T_(pred) may be determined by addingt_(T−PK) to the time of the most recent peak (PK) of the bio-Z signal,where:t_(T−PK)=k0+k1*Δt·pk(n)

The predictive equation we are proposing is based on the fact that thevery most recent cycle times should be negatively weighted. Regressionanalysis supports this approach and indicates a negative weighting isappropriate for accurate prediction of onset. Thus, predicting onset ismore effective if the most recent historical cycle time is incorporatedinto an algorithm with a negative coefficient.

As noted above, stimulation may be delivered for only a portion of therespiratory cycle, such as, for example, during inspiration.Additionally, it may be desirable to begin stimulation approximately 300milliseconds before the onset of inspiration to more closely mimicnormal activation of upper airway dilator muscles. However, predictingand/or measuring inspiration, in particular, the onset of inspiration,may be relatively challenging. Thus, since the onset of expiration maybe relatively easy to measure and/or predict (as discussed in greaterdetail below) when an adequate measure of respiration is available, itis contemplated that stimulation may be triggered as a function ofexpiration onset.

Turning now to FIG. 50A, there is depicted an exemplary respiratorywaveform 5500 for two complete respiratory cycles A and B. In analyzingexemplary waveform 5500, it may be determined that peaks M of thewaveform 5500 may indicate onset of the expiratory phases of respirationcycles A and B. Furthermore, it may be discovered that peaks M occur atregular intervals of approximately 3-4 seconds. Thus, it may berelatively easy to predict the occurrence of subsequent peaks M, andconsequently, the onset of expiration for future respiratory cycles.

Therefore, in order to deliver a stimulus to a patient in accordancewith the principles of the present disclosure, the start of stimulationmay be calculated by first predicting the time intervals between thestart of expiration for subsequently occurring respiratory cycles. Next,in order to capture the entire inspiratory phase, including the briefpre-inspiratory phase of approximately 300 milliseconds, stimulation maybe started at the time N that is prior to the next onset of expirationby approximately 30% to 50% of the time between subsequently occurringexpiratory phases. Stimulating less than 30% or more than 50% prior tothe next expiratory phase may result in an inadequate stimulation periodand muscle fatigue, respectively.

In some embodiments, however, it is contemplated that an adequatemeasure of respiration may not be available, such as, for example, whena relied upon signal has failed. In these embodiments, it iscontemplated that the implanted neurostimulator system may be configuredto respond in one or more of the following three ways. First, theimplanted neurostimulator may completely cease stimulation until anadequate signal is acquired. Second, the neurostimulator may delivercontinuous simulation pulses of predetermined durations (e.g., up to 60seconds) until an adequate signal is acquired; or if an adequate signalis not acquired in this time, the stimulation will be turned off. Third,the neurostimulator may continue to stimulate at the same or a fraction(e.g., one quarter) of the stimulation rate for the most recentlymeasured respiratory cycle. That is to say, the neurostimulator maydeliver stimulation pulses of relatively long durations at a frequencythat is less than the frequency of stimulation utilized with an adequatemeasure of respiration. Alternatively, the neurostimulator may deliverstimulation pulses of relatively short durations at a frequency that isgreater than the frequency used with an adequate measure of respiration.

Description of an Exemplary Stimulation Pulse

Turning now to FIG. 50B, there is depicted an exemplary stimulationpulse waveform 5000 that may be emitted from an INS in accordance withthe principles of the present disclosure. Typically, exemplarystimulation pulse waveform 5000 may include a square wave pulse trainhaving one or more square wave pulses 5001 of approximately 1 to 3 voltsin amplitude, a duration of approximately 100 ms, and a frequency ofapproximately 30 Hz, assuming a 1000 ohm impedance at the electrodes anda constant current or voltage.

In some embodiments, exemplary stimulation pulse waveform 5000 mayinclude a bi-phasic charge balanced waveform square pulses 5001 and5002, as depicted in FIG. 50B. Square pulse 5002 may be included inwaveform 5000 to, among other things, promote efficient stimulationand/or mitigate electrode corrosion. However, square pulse 5002 may beexcluded from waveform 5000 as desired. Furthermore, although thedepicted exemplary waveform 5000 includes square pulse 5002 that exactlybalances the stimulation wave pulse 5001, in certain circumstances,square pulse 5002 may not exactly balance the stimulation wave pulse5001, and may not be a square pulse.

In some embodiments, exemplary stimulation pulse waveform 5000 mayinclude the delivery of a low amplitude (e.g., below the stimulationthreshold), long duration, pre-stimulation pulse 5004. Thepre-stimulation pulse 5004 may include any suitable low amplitude, longduration pulse, and may be provided approximately 0.5 ms before thedelivery of a first stimulation pulse 5001.

Pre-stimulation pulse 5004 may facilitate selectively stimulatingcertain fibers of a nerve, such as, for example, the hypoglossal nerveor the superior laryngeal nerve. In particular, when stimulating thehypoglossal nerve, the presence of a pre-stimulation pulse, such as, forexample, pulse 5004, before a stimulation pulse (e.g., the bi-phasicstimulation pulse 5001 depicted in FIG. 50B) may serve to saturate thelarge diameter fibers of the nerve so as to allow the stimulation pulse5001 to only affect (e.g., stimulate) the smaller diameter fibers of thenerve. In circumstances where a nerve (e.g., the hypoglossal nerve) maybe stimulated for extended periods of time, a pre-stimulation pulse 5004may be selectively introduced to waveform 5000, so as to permitselective switching between stimulating the large and small diameterfibers of the nerve, in order to reduce muscle fatigue. Similarly, insituations where OSA may be treated by stimulating the superiorlaryngeal nerve to open the upper airway through a reflex mechanism, thepresence of pre-stimulation pulse 5004 may serve to saturate the largerdiameter efferent fibers so as to allow the stimulation pulse 5001 toonly affect the smaller diameter afferent fibers of the nerve.

Description of External (Partially Implanted) System

With reference to FIGS. 51A and 51B, an example of an externalneurostimulator system inductively coupled to an internal/implantedreceiver is shown schematically. The system includes internal/implantedcomponents comprising a receiver coil 910, a stimulator lead 60(including lead body 62, proximal connector and distal nerve electrode64). Any of the stimulation lead designs and external sensor designsdescribed in more detail herein may be employed in this genericallyillustrated system, with modifications to position, orientation,arrangement, integration, etc. made as dictated by the particularembodiment employed. The system also includes external componentscomprising a transmit coil 912 (inductively linked to receiver coil 910when in use), an external neurostimulator or external pulse generator920 (ENS or EPG), and one or more external respiratory sensors 916/918.

As illustrated, the receiver coil 910 is implanted in a subcutaneouspocket in the pectoral region and the stimulation lead body 62 istunneled subcutaneously along the platysma in the neck region. The nerveelectrode 64 is attached to the hypoglossal nerve in the submandibularregion.

The transmitter coil 912 may be held in close proximity to the receivercoil 910 by any suitable means such as an adhesive patch, a belt orstrap, or an article of clothing (e.g., shirt, vest, brazier, etc.)donned by the patient. For purposes of illustration, the transmittercoil 912 is shown carried by a t-shirt 915, which also serves to carrythe ENS 920 and respiratory sensor(s) 916, 918. The ENS 920 may bepositioned adjacent the waist or abdomen away from the ribs to avoiddiscomfort while sleeping. The respiratory sensor(s) 916, 918 may bepositioned as a function of the parameter being measured, and in thisembodiment, the sensors are positioned to measure abdominal andthoracic/chest expansion which are indicative of respiratory effort, asurrogate measure for respiration. The external components may beinterconnected by cables 914 carried by the shirt or by wireless means.The shirt may incorporate recloseable pockets for the externalcomponents and the components may be disconnected from the cables suchthat the reusable components may be removed from the garment which maybe disposed or washed.

The transmitting coil antenna 912 and the receiving coil antenna 910 maycomprise air core wire coils with matched wind diameters, number of wireturns and wire gauge. The wire coils may be disposed in a disc-shapedhermetic enclosure comprising a material that does not attenuate theinductive link, such as a polymeric or ceramic material. Thetransmitting coil 912 and the receiving coil 910 may be arranged in aco-axial and parallel fashion for coupling efficiency, but are shownside-by-side for sake of illustration only.

Because power is supplied to the internal components via an inductivelink, the internal components may be chronically implanted without theneed for replacement of an implanted battery, which would otherwiserequire re-operation. Examples of inductively powered implantablestimulators are described in U.S. Pat. No. 6,609,031 to Law et al., U.S.Pat. No. 4,612,934 to Borkan, and U.S. Pat. No. 3,893,463 to Williams,the entire disclosures of which are incorporated herein by reference.

With reference to FIGS. 51C-51G, alternative embodiments of an externalneurostimulator system inductively coupled to an internal/implantedreceiver are schematically shown. These embodiments are similar to theexternal embodiment described above, with a few exceptions. In theseembodiments, the receiver coil 910 is implanted in a positionedproximate the implanted stimulation lead body 62 and nerve electrode 64.The receiver coil 910 may be positioned in a subcutaneous pocket on theplatysma muscle under the mandible, with the lead body 62 tunneling ashort distance to the nerve electrode 64 attached to the hypoglossalnerve. Also in these embodiments, the respiratory sensor(s) 916/918 maybe integrated into the ENS 920 and attached to a conventionalrespiratory belt 922 to measure respiratory effort about the abdomenand/or chest. An external cable 914 connects the ENS 920 to thetransmitter coil 912.

In the embodiment of FIG. 51D, the transmitter coil 912 is carried by anadhesive patch 924 that may be placed on the skin adjacent the receivercoil 910 under the mandible. In the embodiment of FIG. 51E, thetransmitter coil 912 is carried by an under-chin strap 926 worn by thepatient to maintain the position of the transmitter coil 912 adjacentthe receiver coil 910 under the mandible. In the embodiment of FIG. 51F,the receiver coil 910 may be positioned in a subcutaneous pocket on theplatysma muscle in the neck, with the lead body 122 tunneling a slightlygreater distance. The transmitter coil 912 may be carried by a neckstrap 928 worn by the patient to maintain the position of thetransmitter coil 912 adjacent the receiver coil 910 in the neck.

With reference to FIGS. 51G-51K, additional alternative embodiments ofan external neurostimulator system inductively coupled to aninternal/implanted receiver are schematically shown. These embodimentsare similar to the external embodiment described above, with a fewexceptions. As above, the receiver coil 910 may be positioned in asubcutaneous pocket on the platysma muscle under the mandible, with thelead body 62 tunneling a short distance to the nerve electrode 64attached to the hypoglossal nerve. However, in these embodiments, theENS 920 (not shown) may be located remote from the patient such as onthe night stand or headboard adjacent the bed. The ENS 920 may beconnected via a cable 930 to a large transmitter coil 912 that isinductively coupled to the receiver coil 910. The respiratory sensor 916may comprise a conventional respiratory belt 922 sensor to measurerespiratory effort about the abdomen and/or chest, and sensor signalsmay be wirelessly transmitted to the remote ENS 920. As compared toother embodiments described above, the transmitter coil 912 is notcarried by the patient, but rather resides in a proximate carrier suchas a bed pillow, under a mattress, on a headboard, or in a neck pillow,for example. Because the transmitter coil 912 is not as proximate thereceiver coil as in the embodiments described above, the transmittercoil may be driven by a high powered oscillator capable of generatinglarge electromagnetic fields.

As shown in FIG. 51H, the transmitter coil 912 may be disposed in a bedpillow 934. As shown in FIG. 51I, the transmitter coil 912 may comprisea series of overlapping coils disposed in a bed pillow 934 that aresimultaneously driven or selectively driven to maximize energy transferefficiency as a function of changes in body position of the patientcorresponding to changes in position of the receiver coil 910. Thisoverlapping transmitter coil arrangement may also be applied to otherembodiments such as those described previously wherein the transmittercoil is carried by an article donned by the patient. In FIG. 51J, two ormore transmitter coils 912 are carried by orthogonal plates 936 arrangedas shown to create orthogonal electromagnetic fields, thereby increasingenergy transfer efficiency to compensate for movement of the patientcorresponding to changes in position of the receiver coil 910. FIG. 51Jalso illustrates a non-contact respiratory sensor 916 arrangement asutilized for detecting sudden infant death syndrome (SIDS). As shown inFIG. 51K, two orthogonal transmitter coils 912 are located on each sideof a neck pillow 938, which is particularly beneficial for bilateralstimulation wherein a receiver coil 910 may be located on either side ofthe neck.

With reference to FIGS. 51L (front view) and 51M (rear view), externalrespiratory effort sensors 916/918 are schematically shown incorporatedinto a stretchable garment 945 donned by the patient. The sensors916/918 generally include one or more inductive transducers and anelectronics module 942. The inductive transducers may comprise one ormore shaped (e.g., zig-zag or sinusoidal) stranded wires to accommodatestretching and may be carried by (e.g., sewn into) the garment 945 toextend around the patient's abdomen and chest, for example. As thepatient breathes, the patient's chest and/or abdomen expands andcontracts, thus changing the cross-sectional area of the shape (i.e.,hoop) formed by the wire resulting in changes in inductance. Theelectronics module may include an oscillator (LC) circuit with theinductive transducer (L) comprising a part of the circuit. Changes infrequency of the oscillator correspond to changes in inductance of theshaped wires which correlate to respiratory effort. The electronicsmodule may be integrated with an ENS (not shown) or connected to an ENSvia a wired or wireless link for triggering stimulus as describedpreviously.

The garment 945 may include features to minimize movement artifact andaccommodate various body shapes. For example, the garment 945 may beform-fitting and may be sleeveless (e.g., vest) to reduce sensorartifacts due to arm movement. Further, the garment 945 may be tailoredto fit over the patient's hips with a bottom elastic band which helpspull the garment down and keep the sensors 916/918 in the properlocation.

Description of a Specific External (Partially Implanted) Embodiment

With reference to FIGS. 52A-52G a specific embodiment utilizing anexternal neurostimulator system inductively coupled to aninternal/implanted receiver is schematically shown. With initialreference to FIG. 52A, the illustrated hypoglossal nerve stimulatorincludes several major components, namely: an implantable electronicsunit that derives power from an external power source; a stimulationdelivery lead that is anchored to the nerve or adjacent to the nerve andprovides electrical connection between the electronics unit and thenerve, an external (non-implanted) power transmitting device that isinductively coupled with the implant to convey a powering signal andcontrol signals; a power source for the external device that is eithersmall and integrated into the body-worn coil and transmitter or is wiredto the transmitter and transmit induction coil and can be powered byprimary or secondary batteries or can be line powered; and a respiratorysensor such as those described previously.

These components may be configured to provide immediate or delayedactivation of respiration controlled stimulation. Initiation of thestimulation regimen may be by means of activation of an input switch.Visual confirmation can be by an LED that shows adequate signal couplingand that the system is operating and is or will be applying stimulation.As a means of controlling gentleness of stimulation onset and removal,either pulse width ramping of a constant amplitude stimulation signalcan be commanded or amplitude of a constant pulse width stimulationsignal or a combination thereof can be performed.

The electrical stimulation signal is delivered by the stimulation leadthat is connected to the implanted nerve stimulator and attached to orin proximity of a nerve. The implanted electronics unit receives powerthrough a magnetically coupled inductive link. The operating carrierfrequency may be high enough to ensure that several cycles (at least 10)of the carrier, comprise the output pulse. The operating frequency maybe in a band of frequencies approved by governmental agencies for usewith medical instruments operating at high transmitted radio frequency(RF) power (at least 100 milliwatts). For example, the operatingfrequency may be 1.8 MHz, but 13.56 MHz is also a good candidate sinceit is in the ISM (Industrial/Scientific/Medical) band. The non-implanted(external) transmitter device integrates respiration interface, waveformgeneration logic and transmit power driver to drive an induction coil.The power driver generates an oscillating signal that drives thetransmitter induction coil and is designed to directly drive a coil ofcoil reactance that is high enough or can be resonated in combinationwith a capacitor. Power can come from a high internal voltage that isused to directly drive the transmit induction coil or power can comefrom a low voltage source applied to a tap point on the induction coil.

With reference to FIGS. 52B-52E, the waveform generation logic may beused to modulate the carrier in such a way that narrow gaps in thecarrier correspond to narrow stimulation pulses. When stimulator pulsesare not needed, interruptions to the carrier are stopped but the carrieris maintained to ensure that power is immediately available within thestimulator upon demand. Presence or absence of electrical nervestimulation is based on respiration or surrogates thereof. Thetransmitted signal may comprise a carrier of about 1.8 MHz. To controlthe implanted electronics unit to generate individual nerve stimulationpulses, the carrier signal is interrupted. The duration of theinterruption is about equal to the duration of the output stimulationpulse. The stimulation pulses may be about 110 microseconds in durationand are repeated at a rate of approximately 33 per second. In addition,multiple pulses can be transmitted to logic within the implant tocontrol stimulation pulse amplitude, pulse width, polarity, frequencyand structure if needed. Further, onset and removal of stimulation canbe graded to manage patient discomfort from abruptness. Grading maycomprise pulse width control, signal amplitude control or a combinationthereof.

An indicator (not shown) may be used to show when the transmitter isproperly positioned over the implant. The indicator may be a part of thetransmitter or by way of communication with the transmitter, or a partof related patient viewable equipment. Determination of proper positionmay be accomplished by monitoring the transmitter power output loadingrelative to the unloaded power level. Alternatively, the implant receivesignal level transmitted back by a transmitter within the implant may bemonitored to determine proper positioning. Or, the implant receivesignal level that is communicated back to the transmitter by momentarilychanging the loading properties presented to the transmitter, such ashorting out the receive coil may be monitored to determine properpositioning. Such communication may be by means of modulation such aspulse presence, pulse width, pulse-to-pulse interval, multi-pulsecoding.

The transmitter may be powered by an internal primary power source thatis used until it is exhausted, a rechargeable power source or a powersource wired to a base unit. In the case of the wired base unit, powercan be supplied by any combination of battery or line power.

The respiration interface may transduce sensed respiratory activity toan on-off control signal for the transmitter. Onset of stimulation maybe approximately correlated slightly in advance of inspiration and laststhrough the end of inspiration, or onset may be based on anticipation ofthe next respiration cycle from the prior respiration cycle or cycles.The respiration sensor may comprise any one or combination of devicescapable of detecting inspiration. The following are examples: one ormore chest straps; an impedance sensor; an electromyographicalmeasurement of the muscles involved with respiration; a microphone thatis worn or is in proximity to the patients' face; a flow sensor; apressure sensor in combination with a mask to measure flow; and atemperature sensor to detect the difference between cool inspired airversus warmed expired air.

The circuit illustrated in FIG. 52F may be used for the implantedelectronics unit. There are five main subsystems within the design: areceive coil, a power rectifier, a signal rectifier, an output switchand an output regulator. The signal from the inductive link is receivedby L1 which is resonated in combination with C1 and is delivered to boththe power and signal rectifiers. Good coupling consistent with lowtransmitter coil drive occurs when the transmit coil diameter is equalto the receive coil diameter. When coil sizes are matched, couplingdegrades quickly when the coil separation is about one coil diameter. Alarge transmit coil diameter will reduce the criticality of small coilspacing and coil-to-coil coaxial alignment for maximum signal transferat the cost of requiring more input drive power.

The power rectifier may comprise a voltage doubler design to takemaximum advantage of lower signal levels when the transmit to receivecoil spacing is large. The voltage doubler operates with an input ACvoltage that swing negative (below ground potential) causes D1 toconduct and forces C2 to the maximum negative peak potential (minus adiode drop). As the input AC voltage swings away from maximum negative,the node of C2, D1, D2 moves from a diode drop below ground to a diodedrop above ground, forward biasing diode D2. Further upswing of theinput AC voltage causes charge accumulated on C2 to be transferredthrough D2 to C3 and to “pump up” the voltage on C3 on successive ACvoltage cycles. To limit the voltage developed across C3 so that anover-voltage condition will not cause damage, and Zener diode, D3 shuntsC3. Voltage limiting imposed by D3 also limits the output of the signalrectifier section. The power rectifier has a long time constant,compared to the signal rectifier section, of about 10 milliseconds.

The signal rectifier section may be similar in topology to the powerrectifier except that time constants are much shorter—on the order of 10microseconds—to respond with good fidelity to drop-outs in thetransmitted signal. There is an output load of 100K (R1) that imposes acontrolled discharge time constant. Output of the signal rectifier isused to switch Q1, in the output switching section, on and off.

The output switching section compares the potential of C3 to that acrossC5 by means of the Q1, Q2 combination. When there is a gap in thetransmitted signal, the voltage across C5 falls very rapidly incomparison with C3. When the voltage difference between C5 and C3 isabout 1.4 volts, Q1 and Q2 turn on. Q1 and Q2 in combination form a highgain amplifier stage that provides for rapid output switching time. R3is intended to limit the drive current supplied to Q2, and R2 aids indischarging the base of Q2 to improve the turn-off time.

In the output regulator section, the available power rectifier voltageis usually limited by Zener diode D3. When the coil separation becomessuboptimal or too large the power rectifier output voltage will be comevariable as will the switched voltage available at the collector of Q2.For proper nerve stimulation, it may be necessary to regulate the(either) high or variable available voltage to an appropriate level. Anacceptable level is about 3 volts peak. A switched voltage is applied toZener diode D6 through emitter follower Q3 and bias resistor R5. Whenthe switched voltage rises to a level where D6 conducts and developsabout 0.6 volts across R4 and the base-emitter junction of Q4, Q4conducts. o Increased conduction of Q4 is used to remove bias from Q3through negative feedback. Since the level of conduction of Q4 is a verysensitive function of base to emitter voltage, Q4 provides substantialamplification of small variations in D6 current flow and therefore biasvoltage level. The overall result is to regulate the bias voltageapplied to Zener diode D6. Output is taken from the junction of theemitter of Q3 and D6 since that point is well regulated by thecombination of Zener diode breakdown voltage combined with theamplification provided by Q4. In addition to good voltage regulation athe junction of the emitter of Q3 and D6, the output is very tolerant ofload current demand since the conductivity of Q3 will be changed byshifts in the operating point of Q4. Due to amplification by Q3 and Q4,the circuit can drive a range of load resistances. Tolerable loadresistances above 1000 ohms and less than 200 ohms. The regulator hasthe advantage of delivering only the current needed to operate the loadwhile consuming only moderate bias current. Further, bias current isonly drawn during delivery of the stimulation pulse which drops to zerowhen no stimulation is delivered. As a comparison, a simple seriesresistance biased Zener diode requires enough excess current to delivera stimulation pulse and still maintain adequate Zener bias. As a furthercomparison, conventional integrated circuit regulators, such as threeterminal regulators are not designed to well regulate and respondquickly to short input pulses. Experiment shows that three-terminalregulators exhibit significant output overshoot and ramp-up time uponapplication of an input pulse. This can be addressed by applying aconstant bias to a regulator circuit or even moving the regulator beforethe output switching stage but this will be at the cost of constantcurrent drain and subsequently reduced range.

The implanted electronics unit may be used to manage the loss of controland power signals. With this design, more than enough stimulation poweris stored in C3 to supply multiple delivered stimulation pulses. Thisdesign is intended to ensure that the voltage drop is minimal on anyindividual pulse. One of the consequences is that when signal is lost,the circuit treats the condition as a commanded delivery of stimulationand will apply a single, extended duration, energy pulse until the fullstored capacity of C3 is empty. An alternative method may be to use anindirect control modulation to command delivery of a nerve stimulationpulse through logic and provide for a time-out that limits pulseduration.

To stimulate tissue, a modified output stage may be used to mitigateelectrode corrosion and establish balanced charging. The output stage isillustrated in FIG. 52G and includes a capacitive coupling between theground side of the stimulator and tissue interface in addition to ashunt from the active electrode to circuit ground for re-zeroing theoutput coupling capacitor when an output pulse is not being activelydelivered.

Description of Alternative Screening Methods

Screening generally refers to selecting patients that will be responsiveto the therapy, namely neurostimulation of the upper airway dilatornerves and/or muscles such as the hypoglossal nerve that innervates thegenioglossus. Screening may be based on a number of different factorsincluding level of obstruction and critical collapse pressure (Pcrit) ofthe upper airway, for example. Because stimulation of the hypoglossalnerve affects the genioglossus (base of tongue) as well as othermuscles, OSA patients with obstruction at the level of the tongue baseand OSA patients with obstruction at the level of the palate and tonguebase (collectively patients with tongue base involvement) may beselected. Because stimulation of the hypoglossal nerve affects upperairway collapsibility, OSA patients with airways that have a lowcritical collapse pressure (e.g., Pcrit of less than about 5 cm water)may be selected. Pcrit may be measured using pressure transducers in theupper airway and measuring the pressure just prior to an apnea event(airway collapse). Alternatively, a surrogate for Pcrit such as CPAPpressure may be used. In this alternative, the lowest CPAP pressure atwhich apnea events are mitigated may correlate to Pcrit.

The critical collapse pressure (Pcrit) may be defined as the pressure atwhich the upper airway collapses and limits flow to a maximal level.Thus, Pcrit is a measure of airway collapsibility and depends on thestability of the walls defining the upper airway as well as thesurrounding pressure. Pcrit may be more accurately defined as thepressure inside the upper airway at the onset of flow limitation whenthe upper airway collapses. Pcrit may be expressed as:Pcrit=Pin−Pout

where

Pin=pressure inside the upper airway at the moment of airway collapse;and

Pout=pressure outside the upper airway (e.g., atmospheric pressure).

Other screening methods and tools may be employed as well. For example,screening may be accomplished through acute testing of tongue protrudermuscle contraction using percutaneous fine wire electrodes inserted intothe genioglossus muscle, delivering stimulus and measuring one or moreof several variables including the amount of change in critical openingpressure, the amount of change in airway caliber, the displacement ofthe tongue base, and/or the retraction force of the tongue (as measuredwith a displacement and/or force gauge). For example, a device similarto a CPAP machine can be used to seal against the face (mask) andcontrol inlet pressure down to where the tongue and upper airwaycollapse and occlude during inspiration. This measurement can berepeated while the patient is receiving stimulation of the geneoglossusmuscle (or other muscles involved with the patency of the upper airway).Patients may be indicated for the stimulation therapy if the differencein critical pressure (stimulated vs. non-stimulated) is above athreshold level.

Similarly, a flexible optical scope may be used to observe the upperairway, having been inserted through the mask and nasal passage. Thedifference in upper airway caliber between stimulation andnon-stimulation may be used as an inclusion criterion for the therapy.The measurement may be taken with the inlet air pressure to the patientestablished at a pre-determined level below atmospheric pressure tobetter assess the effectiveness of the stimulation therapy.

Another screening technique involves assessing the protrusion force ofthe tongue upon anterior displacement or movement of the tongue with andwithout stimulation while the patient is supine and (possibly) sedatedor asleep. A minimum increase in protrusion force while understimulation may be a basis for patient selection.

For example, with reference to FIG. 53, a non-invasive oral appliance530 may be worn by the patient during a sleep study that can directlymeasure the protrusion force of the tongue as a basis for patientselection. The oral appliance 530 may include a displacement probe 532for measuring tongue movement protrusion force by deflection (D). Theoral appliance 530 may also include a force sensor 534 for measuring theforce (F) applied by protrusion of the tongue. The sensors in thedisplacement probe 532 and the force sensor 534 may be connected tomeasurement apparatus by wires 536.

FIG. 54 illustrates another example of a non-invasive oral appliance 540that may be worn by the patient during a sleep study to directly measurethe protrusion force of the tongue as a basis for patient selection. Theoral appliance 540 includes a displacement sensor 542 for measuringtongue movement and a force sensor for measuring tongue protrusionforce. The displacement sensor and the force sensor may be connected tomeasurement apparatus by wires 546.

Oral appliances 530 and 540 could be worn during a sleep study and wouldmeasure the tongue protrusion force during (and just prior to) an apneaevent when the protruder muscle tone is presumed to be inadequate tomaintain upper airway patency. The protrusion force measured as theapnea is resolved by the patient will increase as the patient changessleep state and the airway again becomes patent. The force differencemay be used as a basis for patient selection.

Another screening technique involves the use of an oral appliance withsub-lingual surface electrodes contacting the base of the tongue or finewire electrodes inserted into the genioglossus muscle to stimulate thetongue protruder muscle(s) synchronous with respiration during a sleepstudy. The oral appliance may be fitted with a drug delivery system(e.g., drug eluting coating, elastomeric pump, electronically controlledpump) for topical anesthesia to relieve the discomfort of theelectrodes.

For example, with reference to FIG. 55, an oral appliance 550 includes apair of small needle intramuscular electrodes 552 that extend into thegenioglossus. The electrodes 552 are carried by flexible wires 554 andmay be coupled to an external pulse generator (not shown) by wires 556.The electrodes 552 may be supported by a drug (e.g., anesthetic) elutingpolymeric member 558.

Alternatively, with reference to FIG. 56, an oral appliance 560 includesa cathode electrode 562 guarded by two anode electrodes 564 carried by asoft extension 565 that extends under the tongue. The surface electrodes562 and 564 contact the floor of the mouth under the tongue toindirectly stimulate the genioglossus. The electrodes 562 and 564 may becoupled to an external pulse generator (not shown) by wires 566. Theextension 565 may incorporate holes 568 through which a drug (e.g.,anesthetic) may be eluted.

Oral appliances 550 and 560 may be used during a sleep study andstimulation of the target tissue can be performed synchronous withrespiration and while inlet airflow pressure can be modulated. Theability to prevent apneas/hypopneas can be directly determined. Also thecritical opening pressure with and without stimulation can bedetermined. Alternatively or in addition, the intramuscular or surfaceelectrodes may be used to measure genioglossus EMG activity, either withor without stimulation. On any of theses bases, patient selection may bemade.

Patient selection may also be applied to the respiratory sensors todetermine if the respiratory sensors will adequately detect respirationfor triggering stimulation. For example, in the embodiment wherein bio-Zis used to detect respiration using an implanted lead 70, skin surfaceor shallow needle electrodes may be used prior to implantation todetermine if the signal will be adequate. This method may also be suedto determine the preferred position of the electrodes (i.e., optimalbio-Z vector). This may be done while the patient is sleeping (i.e.,during a sleep study) or while the patient is awake.

Description of Alternative Intra-Operative Tools

Intra-operatively, it may be desirable to determine the correct portionof the nerve to stimulate in order to activate the correct muscle(s) andimplant the nerve cuff electrode accordingly. Determining the correctposition may involve stimulating at different locations along the lengthor circumference of the nerve and observing the effect (e.g., tongueprotrusion). In addition or in the alternative, and particularly in thecase of field steering where multiple combinations of electrode contactsare possible, it may be desirable to determine optimal electrode orfiled shape combinations.

An example of an intra-operative stimulating tool 570 is shown in FIGS.57A and 57B. In this embodiment, the tool 570 includes a first shaft 571with a distal half-cuff 573. Tool 570 further includes a second shaft575 with a proximal movable collar 574 and a distal half-cuff 575.Stimulating tool 570 includes multiple electrodes 572 on half-cuff 573and/or half-cuff 575 that may be arranged in an array or matrix as shownin FIG. 57C, which is a view taken along line A-A in FIG. 57B. Thehalf-cuffs 573 and 575 may be longitudinally separated for placementabout a nerve and subsequently closed such that the half-cuffs 573 and575 gently grasp the nerve. The electrodes 575 may be sequenced througha series of electrode/field shape combinations to optimize (lower) thecritical opening pressure, airway caliber, tongue protrusion force orother acute indicia of therapeutic efficacy.

The tool 570 may be part of an intra-operative system including: (1)tool 570 or other tool with one or more stimulating electrodes that aredesigned to be easily handled by the surgeon during implant surgery; (2)an external pulse generator which triggers off of a respiration signal;(3) a feedback diagnostic device that can measure critical closingpressure intra-operatively; and (4) an algorithm (e.g., firmware orsoftware in the programmer) that is design to automatically or manuallysequence through a series of electrode configurations that will identifythe best placement of electrode cuffs on the nerves and configuration ofelectrode polarity and amplitude settings. Information from theintra-operative system may greatly speed the process of identifyingwhere to place the electrode cuff(s) on the hypoglossal nerve and whatfield steering may be optimal or necessary to provide efficacy.

In certain circumstances, such as, when treating a child or a smalladult, it may be difficult to implant a nerve cuff electrode of thepresent disclosure about a nerve in a patient's body. Accordingly, itmay be desirable to provide a tool capable of facilitating temporaryexpansion of a nerve cuff electrode of the present disclosure, so as toslip the nerve cuff electrode around a patient's nerve. Turning now toFIGS. 58A-58B, there is depicted a tool 5800 for temporarily expanding anerve cuff electrode in accordance with the principles of the presentdisclosure. Tool 5800 may include a substantially scissor-likeconfiguration having a first element 5801 and a second element 5802pivotably secured together by a suitable fastener, such as, for example,pivot pin 5803, acting as a fulcrum. Elements 5801 and 5802 may besubstantially similar to each other or may differ as necessary. In thedepicted embodiment, elements 5801 and 5802 may include levers havingdistal effecting portions 5804, 5805 and proximal actuating portions5806, 5807.

Proximal actuating portions 5806, 5807 may be of any suitable length andmay be connected to respective handles (not shown), which may be used tooperate tool 5800. Alternatively, proximal actuating portions 5806, 5807themselves may be used to operate tool 5800. Distal effecting portions5804, 5805 may include any suitable configuration to achieve the desiredeffect. For example, each portion 5804, 5805 may include a substantiallycurved configuration. Additionally, a distal end of each portion 5804,5805 may be provided with a fastening mechanism, such as, for example,hook-like projection 5804a, 5805a, for facilitating connection of tool5800 to a nerve cuff electrode. As shown in FIGS. 58A-58B, hook-likeprojections 5804a, 5805a may be configured to be disposed in differingparallel planes, such that projections 5804a, 5805a may be spaced(offset) horizontally from one another. In use, distal effectingportions 5804, 5805 may be opened and closed as proximal actuatingportions 5806, 5807 may be rotated about pivot pin 5803.

In embodiments where tool 5800 may be used to temporarily expand a nervecuff electrode for implantation purposes, the nerve cuff electrode,e.g., nerve cuff electrode 5810, may be provided with one more geometricconfigurations for facilitation connection with tool 5800. In thedepicted embodiment, nerve cuff electrode 5810 may be provided withextensions 5811, 5812 for facilitating connection with tool 5800. Eachextension 5811, 5812 may be provided with openings 5811a, 5812a,respectively, for receiving hook-like projections 5804a, 5805a, so as tooperably couple nerve cuff electrode 5811 with tool 5800.

Description of Miscellaneous Alternatives

The implanted neurostimulation system may be configured so thatstimulation of the nerve is set at a relatively low level (i.e., lowvoltage amplitude, narrow pulse width, lower frequency) so as tomaximize battery life of the INS and to minimize the chances that theelectrical stimulation will cause arousal from sleep. Ifapneas/hypopneas are detected, then the electrical stimulation can beincreased progressively until the apneas/hypopneas are no longerdetected, up to a maximum pre-set stimulation level. This auto titrationmay automatically be reset to the low level after the patient isawakened and sits up (position detector) or manually reset using thepatient controller. The stimulation level may be automatically reducedafter a period of time has elapsed with no (or few) apneas/hypopneasdetected.

The stimulation level (i.e., voltage amplitude, pulse width, frequency)may be adjusted based on changes in respiration rate. Respiration rateor patterns of rate change may be indicative of sleep state. A differentpower level based on sleep state may be used for minimal powerconsumption, minimal unwanted stimulation (sensory response), etc.,while providing adequate efficacy.

The electrical field shape used to stimulate the target nerve can bechanged while the system is proving therapy based on feedback indicatingthe presence (or lack) of apneas/hypopneas. The electrical field shapefor an implanted system can be changed by adjusting the polarity,amplitude and other stimulation intensity parameters for each of theelectrodes within the nerve stimulating cuff. An algorithm within theINS may change the currently operating electrical field shape if thepresence of apneas/hypopneas is detected, and then wait a set period oftime to determine if the new configuration was successful in mitigatingthe apneas/hypopneas before adjusting the field shape again.Additionally, the system may be designed to keep a log of the mostsuccessful stimulation patterns and when they were most likely to beeffective. This may allow the system to “learn” which settings to beused during what part of the night, for example, or with specificbreathing patterns or cardiac signal patterns or combinations thereof.

The proportion of stimulation intensity of two electrode cuffs used tostimulate a nerve can be modulated while the system is providing therapybased on feedback indicating the presence (or lack) of apneas/hypopneas.For example, one nerve stimulating electrode cuff may be place on themore proximal section of the hypoglossal nerve, while a second is placedmore distally. The proximal cuff will be more likely to stimulatebranches of the hypoglossal nerve going to muscles in the upper airwayinvolved with tongue or hyoid retrusion while the more distal electrodecuff will more likely stimulate only the muscles involved withtongue/hyoid protrusion. Research suggests that to best maintain upperairway patency, stimulating both protrudes and retruders (in the rightproportion) may be more effective that stimulating protruders alone.Software within the INS may change the currently operating proportion ofelectrical stimulation going to the distal electrode cuff in proportionto that going to the proximal cuff based on the presence ofapneas/hypopneas detected. The system may then wait a set period of timeto determine if the new configuration was successful in mitigating theapneas/hypopneas before adjusting the system again. Additionally, thesystem software may be designed to keep a log of the most successfulstimulation proportion and when they were most likely to be effective.This may allow the system to “learn” which settings to be used duringwhat part of the night, for example, or with specific breathing patternsor cardiac signal patterns or combinations thereof.

The system described above may modulate electrical stimulation intensityproportion based on electromyogram (EMG) feedback from the muscles inthe upper airway being stimulated or others in the area. This feedbackmay be used to determine the correct proportion of stimulation betweenprotruders and retruders. The correct ratio of EMG activity betweenretruders and protruders may be determined during a sleep study for anindividual, may be determined to be a constant for a class of patientsor may be “learned” my the implanted system by using the detection ofapneas/hypopneas as feedback.

A library of electrical stimulation parameter settings can be programmedinto the INS. These settings listed in the library may be selected bythe patient manually using the patient programmer based on, for example:(1) direct patient perception of comfort during stimulation; (2) a logof the most successful settings compiled by the software in the INS(assumes apnea/hypopnea detection capability); (3) a sleep physician'sor technician's assessment of the most effective stimulation asdetermined during a sleep study; and/or (4) a list of the most effectiveparameters produced for a particular class of patient or other.

The electrical stimulation parameters described above may be adjustedbased on patient position as detected by a position sensor within theINS. The best setting for a given position may be determined by, forexample: (1) a log of the most successful settings compiled or learnedby the software in the INS (assumes apnea/hypopnea detectioncapability); (2) a sleep physician's or technician's assessment of themost effective stimulation as determined during a sleep study; and/or(3) a list of the most effective parameters produced for a particularclass of patient or other.

To avoid fatigue using a normal duty cycle or to extend the time thatthe upper airway is opened through neurostimulation, different parts ofthe genioglossus muscle and/or different muscles involved withestablishing patency of the upper airway can be alternately stimulated.For example, using two or more nerve or muscle electrode cuffs, the leftand right side genioglossus muscles can be alternately stimulated,cutting the effective duty cycle on each muscle in half. In addition,different protruder muscles on the ipsilateral side such as thegeniohyoid and the genioglossus muscle can be alternately stimulated tothe same effect. This may also be accomplished through one electrodecuff using field steering methods that selectively stimulated thefascicles of the hypoglossal nerve going to one group of protrudersalternating with stimulating the fascicles leading to a differentprotruder muscle group. This method may also be used to alternatelystimulate one group of muscle fibers within the genioglossus muscle withthe compliment of muscle fibers in the same muscle group.

To increase the ability of the upper airway to open during a (sensed)apnea/hypopnea through neurostimulation, different parts of thegenioglossus muscle and/or different muscles involved with establishingpatency of the upper airway can be simultaneously stimulated. Forexample, using two or more nerve or muscle electrode cuffs, the left andright side genioglossus muscles can be simultaneously stimulated,greatly increasing the protrusion forces. In addition, differentprotruder muscles on the ipsilateral side such as the geneohyoid and thegenioglossus muscle can be simultaneously stimulated to the same effect.This may also be accomplished through one electrode cuff using fieldsteering methods that selectively stimulated the fascicles of thehypoglossal nerve going to one group of protruders simultaneously withstimulating the fascicles leading to a different protruder muscle group.This may be achieved with one electrode cuff using field steering on amore proximal location on the hypoglossal nerve or two or more electrodecuffs, one on each branch going to a muscle involved with maintainingmuscle patency.

A sensor inside the INS (or elsewhere in system implanted) may detectbody position and automatically shut off stimulation when patient sitsup or stands up. This will prevent unwanted stimulation when patient isno longer sleeping. The device may automatically restart the stimulationafter the sensor indicates the patient is again horizontal, with orwithout a delay. The system may also be configured so that thestimulation can only be restarted using the patient controller, with, orwithout a delay.

The respiration signal using impedance and/or EMG/ENG are easily capableof determining heart rate. The stimulation may be interrupted or turnedoff when the heart rate falls outside out a pre-determined acceptablerange. This may be an effective safety measure that will decrease thechance that hypoglossal nerve stimulation will interfere with mitigatingphysiological processes or interventional emergent medical procedures.

Respiration waveforms indicating apneas/hypopneas or of other clinicalinterest may be recorded and automatically telemetered to a bed-sidereceiver unit or patient programmer. Respiration waveforms indicatingfrequent apneas/hypopneas, abnormal breathing patterns, irregular heartrate/rhythm may be recorded and automatically telemetered to a bed-sidedeceiver unit or patient programmer causing an alarm to be issued(audible/visible). The INS status such as low battery or systemmalfunction may also trigger an alarm.

Electrical stimulation intensity could be ramped up for each respirationcycle by increasing amplitude or pulse width from 0 to a set point toprevent sudden tongue protrusion or sudden airway opening causing thepatient to wake up. During inspiration, the system may deliverapproximately 30 pulses per second for a length of time of one to oneand one half seconds, totaling between about 30 and 45 pulses perrespiration cycle. Prior to delivery of these 30 to 45 pulses, amplitudeof each individual therapy pulse (in an added group of pulses) could beramped up from 0 to a set point at a rate of <10% of the amplitudeintended for the active duty cycle or 200 mS, whichever is less. Thepulse width of each individual therapy pulse could be ramped up from 0to a set point at a rate of <10% of the active duty cycle or 200 mS,whichever is less. Each of these ramp methods would require a predictivealgorithm that would stimulate based on the previous inspiration cycle.

Nerves innervating muscles that are involved with inspiration, such asthe hypoglossal nerve, have been shown to have greater electricalactivity during apnea or hypopnea. This signal cannot be easily measuredwhile simultaneously stimulating the same nerve. One method ofstimulating and sensing using the same lead is to interleave a sensingperiod within the stimulation pulse bursts during the duty cycle. Inother words, the sensing period may occur between pulses within thestimulation pulse train. This approach may be used with electrodes/leadsthat directly stimulate and alternately sense on a nerve involved withinspiration or on a muscle involved with inspiration or a combination ofthe two. The approach may allow sensing of apnea/hypopnea, as well astherapeutic stimulation.

From the foregoing, it will be apparent to those skilled in the art thatthe present invention provides, in exemplary non-limiting embodiments,devices and methods for nerve stimulation for OSA therapy. Further,those skilled in the art will recognize that the present invention maybe manifested in a variety of forms other than the specific embodimentsdescribed and contemplated herein. Accordingly, departures in form anddetail may be made without departing from the scope and spirit of thepresent invention as described in the appended claims.

What is claimed is:
 1. A method of maintaining patency of an upperairway of a patient to treat obstructive sleep apnea, the methodcomprising: sensing a biological parameter indicative of respiration,wherein the biological parameter includes impedance; analyzing thebiological parameter to identify onsets of expiration; calculating arespiratory period from the onsets of expiration; predicting an onset ofa future expiratory phase; and beginning stimulation of a nerve afraction of the calculated respiratory period before the onset of thefuture expiratory phase, and continuing stimulation of the nerve duringan entire inspiratory phase, wherein the method is performed withoutidentifying an onset of the inspiratory phase.
 2. The method of claim 1,wherein the nerve is an internal branch of a superior laryngeal nerve.3. The method of claim 1, further comprising: implanting an impedancesensor within the patient, wherein the impedance sensor is coupled to anelectrical stimulator by a sensing lead.
 4. The method of claim 1,wherein beginning stimulation of the nerve includes deliveringelectrical stimulation to one of a hypoglossal nerve and aglossopharyngeal nerve.
 5. The method of claim 4, further comprisingdelivering stimulation to a portion of a superior laryngeal nerveconcurrently with the stimulation delivered to the one of a hypoglossalnerve and a glossopharyngeal nerve.
 6. The method of claim 1, furthercomprising: steering an electrical field of a nerve cuff to stimulateonly afferent fibers of the nerve.
 7. The method of claim 1, wherein thestep of beginning stimulation of a nerve includes delivering stimulationto only afferent fibers of an internal branch of a superior laryngealnerve.
 8. The method of claim 1, wherein the stimulation is deliveredvia a nerve cuff connected to an electrical stimulator via a stimulationlead including a portion having a serpentine configuration.
 9. Themethod of claim 8, wherein the stimulation lead includes a portionconfigured to be secured to a body structure other than a nerve.
 10. Themethod of claim 8, wherein the nerve cuff includes a plurality ofelectrodes in direct contact with the nerve.
 11. The method of claim 1,further comprising: an electrode sensor for wherein the step of sensingthe biological parameter, wherein the electrode sensor is performed viaan electrode sensor coupled to sensing circuitry of an electricalstimulator, wherein stimulation of the nerve includes delivering anelectrical stimulation to a glossopharyngeal nerve via a nerve cuffhaving a plurality of electrodes, wherein the nerve cuff is connectedto-the to the electrical stimulator by a stimulation lead, and wherein aportion of the stimulation lead is configured to elongate in response tomovement by the patient.
 12. The method of claim 11, wherein thestimulation lead further includes a portion configured to be secured toa body structure other than a nerve.
 13. The method of claim 1, whereinthe stimulation is delivered to the nerve via a nerve cuff connected toan electrical stimulator, the nerve cuff comprising: a base memberextending from a first side wall to a second side wall and having a topwall and a bottom wall; a first member extending from the first sidewall; a second member extending from the second side wall; and a thirdmember having a first end fixedly engaged to the first side walladjacent the first member, wherein the third member extends over the topwall of the base member, the second member extends over the top wall ofthe base member, and the first member, the second member, and the thirdmember define a lumen.
 14. The method of claim 13, wherein the thirdmember is capable of transitioning between a first position, prior topositioning of the electrode cuff about a nerve, and a second positionsubsequent to the positioning of the electrode cuff about the nerve,wherein the third member is positioned a first distance above the topwall of the base member in the first position, and the third member ispositioned a second distance smaller than the first distance above thetop wall of the base member in the second position.
 15. The method ofclaim 13, wherein the second member is capable of transitioning betweena first position, prior to positioning of the electrode cuff about anerve, and a second position subsequent to the positioning of theelectrode cuff about the nerve, wherein the second member is positioneda first distance above the top wall of the base member in the firstposition, and the second member is positioned a second distance, greaterthan the first distance, above the top wall of the base member in thesecond position.
 16. The method of claim 13, wherein the second memberhas a first thickness at a first end of the second member and a secondthickness, less than the first thickness, at a second end.
 17. A methodof treating obstructive sleep apnea by innervating a mechanoreceptorwithin a patient's upper airway via stimulating a superior laryngealnerve including both afferent and efferent fibers, the methodcomprising: chronically implanting a nerve cuff adjacent a portion of asuperior laryngeal nerve:; sensing a biological parameter indicative ofrespiration, wherein the biological parameter includes impedance;analyzing the sensed biological parameter to identify onsets ofexpiration; calculating a respiratory period from the onsets ofexpiration; predicting the onset of a future expiratory phase; andbeginning stimulation of the superior laryngeal nerve a fraction of thecalculated respiratory period before the onset of the future expiratoryphase, and continuing stimulation of the superior laryngeal nerve duringan entire inspiratory phase, wherein the method is performed withoutidentifying an onset of the inspiratory phase.
 18. The method of claim17, further comprising: delivering an electrical stimulation to one of ahypoglossal nerve and a glossopharyngeal nerve simultaneously with thestimulation to the superior laryngeal nerve.
 19. The method of claim 17,further comprising: steering an electrical field of the nerve cuff tostimulate only the afferent fibers of an internal branch of the superiorlaryngeal nerve.
 20. The method of claim 17, wherein the nerve cuffincludes a plurality of electrodes in direct contact with a surface ofthe superior laryngeal nerve.
 21. A method of treating obstructive sleepapnea, the method comprising: chronically implanting a nerve cuffadjacent a portion of a superior laryngeal nerve; sensing a biologicalparameter indicative of respiration, wherein the biological parameterincludes impedance; analyzing the biological parameter to identifyonsets of expiration; calculating a respiratory period from the onsetsof expiration; predicting an onset of a future expiratory phase; andbeginning stimulation of the superior laryngeal nerve a fraction of thecalculated respiratory period before the onset of the future expiratoryphase, and continuing stimulation of the superior laryngeal nerve duringan entire inspiratory phase, wherein the method is performed withoutidentifying an onset of the inspiratory phase.
 22. A method of treatingobstructive sleep apnea, the method comprising: sensing a biologicalparameter indicative of respiration, wherein the biological parameterincludes impedance; analyzing the biological parameter to identifyonsets of expiration; calculating a respiratory period from the onsetsof expiration; predicting an onset of a future expiratory phase; andbeginning stimulation of a nerve a fraction of the calculatedrespiratory period before the onset of the future expiratory phase, andcontinuing stimulation of the nerve during an entire inspiratory phase,wherein the method is performed without identifying an onset of theinspiratory phase.
 23. The method of claim 1, further comprisingsteering an electrical field of a nerve cuff to stimulate fibers of thenerve, wherein a majority of the stimulated fibers of the nervecomprises afferent fibers.
 24. The method of claim 1, wherein beginningstimulation of the nerve includes delivering stimulation to fibers of aninternal branch of a superior laryngeal nerve, and wherein a majority ofthe fibers to which stimulation is delivered comprises afferent fibers.25. The method of claim 17, further comprising steering an electricalfield of the nerve cuff to stimulate fibers of an internal branch of thesuperior laryngeal nerve, wherein a majority of the stimulated fibers ofthe nerve comprises afferent fibers.